BRCA2 reversion mutation–independent resistance to PARP inhibition through impaired DNA prereplication complex function Article Swipe
Kyrie Pappas
,
Matteo Ferrari
,
Perianne Smith
,
Subhiksha Nandakumar
,
Zahra Khan
,
Serina B. Young
,
Justin LaClair
,
Marco Vincenzo Russo
,
Emmet Huang-Hobbs
,
Nikolaus Schultz
,
Wassim Abida
,
Wouter R. Karthaus
,
Maria Jasin
,
Charles L. Sawyers
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2426743122
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2426743122
Recent approvals of polymeric adenosine diphosphate ribose (poly(ADP-ribose) polymerase inhibitors (PARPi) for BRCA-mutant metastatic castration resistant prostate cancer necessitate an understanding of the factors that shape sensitivity and resistance. Reversion mutations that restore homologous recombination (HR) repair are detected in ~50 to 80% of BRCA-mutant patients who respond but subsequently relapse, but there is currently little insight into why only ~50% of BRCA-mutant patients display upfront resistance. To address this question, we performed a genome-wide CRISPR screen to identify genomic determinants of PARPi resistance in murine Brca2 Δ/Δ prostate organoids genetically engineered in a manner that precludes the development of reversion mutations. Remarkably, we recovered multiple independent single guide RNAs (sgRNAs) targeting three different members ( Cdt1, Cdc6, and Dbf4 ) of the DNA prereplication complex (pre-RC), each of which independently conferred resistance to olaparib and the next-generation PARP-1 selective inhibitor AZD5305. Moreover, sensitivity to PARP inhibition was restored in Brca2 Δ/Δ , Cdc6-depleted prostate cells by knockdown of geminin, a negative regulator of Cdt1, further implicating the critical role of a functional pre-RC complex in PARPi sensitivity. Furthermore, ~50% of CRPC tumors have copy number loss of pre-RC complex genes, particularly CDT1 . Mechanistically, prostate cells with impaired pre-RC activity displayed rapid resolution of olaparib-induced DNA damage as well as protection from replication fork degradation caused by Brca2 loss, providing insight into how Brca2-mutant cancer cells can escape cell death from replication stress induced by PARP inhibition in the absence of HR repair. Of note, a pharmacologic inhibitor that targets the CDT1/geminin complex (AF615) restored sensitivity to AZD5305, providing a potential translational avenue to enhance sensitivity to PARP inhibition.
Related Topics
Concepts
Reversion
Mutation
Genetics
Resistance (ecology)
Function (biology)
Poly ADP ribose polymerase
DNA
Biology
Cancer research
Phenotype
Gene
Polymerase
Ecology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1073/pnas.2426743122
- https://www.pnas.org/doi/pdf/10.1073/pnas.2426743122
- OA Status
- hybrid
- Cited By
- 2
- References
- 42
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4410988143
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4410988143Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1073/pnas.2426743122Digital Object Identifier
- Title
-
BRCA2 reversion mutation–independent resistance to PARP inhibition through impaired DNA prereplication complex functionWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-06-03Full publication date if available
- Authors
-
Kyrie Pappas, Matteo Ferrari, Perianne Smith, Subhiksha Nandakumar, Zahra Khan, Serina B. Young, Justin LaClair, Marco Vincenzo Russo, Emmet Huang-Hobbs, Nikolaus Schultz, Wassim Abida, Wouter R. Karthaus, Maria Jasin, Charles L. SawyersList of authors in order
- Landing page
-
https://doi.org/10.1073/pnas.2426743122Publisher landing page
- PDF URL
-
https://www.pnas.org/doi/pdf/10.1073/pnas.2426743122Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
-
https://www.pnas.org/doi/pdf/10.1073/pnas.2426743122Direct OA link when available
- Concepts
-
Reversion, Mutation, Genetics, Resistance (ecology), Function (biology), Poly ADP ribose polymerase, DNA, Biology, Cancer research, Phenotype, Gene, Polymerase, EcologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
2Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2Per-year citation counts (last 5 years)
- References (count)
-
42Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
Full payload
| id | https://openalex.org/W4410988143 |
|---|---|
| doi | https://doi.org/10.1073/pnas.2426743122 |
| ids.doi | https://doi.org/10.1073/pnas.2426743122 |
| ids.pmid | https://pubmed.ncbi.nlm.nih.gov/40460119 |
| ids.openalex | https://openalex.org/W4410988143 |
| fwci | 6.54107818 |
| mesh[0].qualifier_ui | Q000494 |
| mesh[0].descriptor_ui | D000067856 |
| mesh[0].is_major_topic | True |
| mesh[0].qualifier_name | pharmacology |
| mesh[0].descriptor_name | Poly(ADP-ribose) Polymerase Inhibitors |
| mesh[1].qualifier_ui | |
| mesh[1].descriptor_ui | D000818 |
| mesh[1].is_major_topic | False |
| mesh[1].qualifier_name | |
| mesh[1].descriptor_name | Animals |
| mesh[2].qualifier_ui | |
| mesh[2].descriptor_ui | D008297 |
| mesh[2].is_major_topic | False |
| mesh[2].qualifier_name | |
| mesh[2].descriptor_name | Male |
| mesh[3].qualifier_ui | |
| mesh[3].descriptor_ui | D051379 |
| mesh[3].is_major_topic | False |
| mesh[3].qualifier_name | |
| mesh[3].descriptor_name | Mice |
| mesh[4].qualifier_ui | Q000235 |
| mesh[4].descriptor_ui | D019008 |
| mesh[4].is_major_topic | True |
| mesh[4].qualifier_name | genetics |
| mesh[4].descriptor_name | Drug Resistance, Neoplasm |
| mesh[5].qualifier_ui | Q000235 |
| mesh[5].descriptor_ui | D024682 |
| mesh[5].is_major_topic | True |
| mesh[5].qualifier_name | genetics |
| mesh[5].descriptor_name | BRCA2 Protein |
| mesh[6].qualifier_ui | Q000378 |
| mesh[6].descriptor_ui | D024682 |
| mesh[6].is_major_topic | True |
| mesh[6].qualifier_name | metabolism |
| mesh[6].descriptor_name | BRCA2 Protein |
| mesh[7].qualifier_ui | Q000494 |
| mesh[7].descriptor_ui | D010793 |
| mesh[7].is_major_topic | False |
| mesh[7].qualifier_name | pharmacology |
| mesh[7].descriptor_name | Phthalazines |
| mesh[8].qualifier_ui | |
| mesh[8].descriptor_ui | D006801 |
| mesh[8].is_major_topic | False |
| mesh[8].qualifier_name | |
| mesh[8].descriptor_name | Humans |
| mesh[9].qualifier_ui | Q000494 |
| mesh[9].descriptor_ui | D010879 |
| mesh[9].is_major_topic | False |
| mesh[9].qualifier_name | pharmacology |
| mesh[9].descriptor_name | Piperazines |
| mesh[10].qualifier_ui | |
| mesh[10].descriptor_ui | D009154 |
| mesh[10].is_major_topic | False |
| mesh[10].qualifier_name | |
| mesh[10].descriptor_name | Mutation |
| mesh[11].qualifier_ui | Q000235 |
| mesh[11].descriptor_ui | D018797 |
| mesh[11].is_major_topic | False |
| mesh[11].qualifier_name | genetics |
| mesh[11].descriptor_name | Cell Cycle Proteins |
| mesh[12].qualifier_ui | Q000378 |
| mesh[12].descriptor_ui | D018797 |
| mesh[12].is_major_topic | False |
| mesh[12].qualifier_name | metabolism |
| mesh[12].descriptor_name | Cell Cycle Proteins |
| mesh[13].qualifier_ui | Q000187 |
| mesh[13].descriptor_ui | D004261 |
| mesh[13].is_major_topic | False |
| mesh[13].qualifier_name | drug effects |
| mesh[13].descriptor_name | DNA Replication |
| mesh[14].qualifier_ui | Q000235 |
| mesh[14].descriptor_ui | D064129 |
| mesh[14].is_major_topic | False |
| mesh[14].qualifier_name | genetics |
| mesh[14].descriptor_name | Prostatic Neoplasms, Castration-Resistant |
| mesh[15].qualifier_ui | Q000188 |
| mesh[15].descriptor_ui | D064129 |
| mesh[15].is_major_topic | False |
| mesh[15].qualifier_name | drug therapy |
| mesh[15].descriptor_name | Prostatic Neoplasms, Castration-Resistant |
| mesh[16].qualifier_ui | Q000494 |
| mesh[16].descriptor_ui | D000067856 |
| mesh[16].is_major_topic | True |
| mesh[16].qualifier_name | pharmacology |
| mesh[16].descriptor_name | Poly(ADP-ribose) Polymerase Inhibitors |
| mesh[17].qualifier_ui | |
| mesh[17].descriptor_ui | D000818 |
| mesh[17].is_major_topic | False |
| mesh[17].qualifier_name | |
| mesh[17].descriptor_name | Animals |
| mesh[18].qualifier_ui | |
| mesh[18].descriptor_ui | D008297 |
| mesh[18].is_major_topic | False |
| mesh[18].qualifier_name | |
| mesh[18].descriptor_name | Male |
| mesh[19].qualifier_ui | |
| mesh[19].descriptor_ui | D051379 |
| mesh[19].is_major_topic | False |
| mesh[19].qualifier_name | |
| mesh[19].descriptor_name | Mice |
| mesh[20].qualifier_ui | Q000235 |
| mesh[20].descriptor_ui | D019008 |
| mesh[20].is_major_topic | True |
| mesh[20].qualifier_name | genetics |
| mesh[20].descriptor_name | Drug Resistance, Neoplasm |
| mesh[21].qualifier_ui | Q000235 |
| mesh[21].descriptor_ui | D024682 |
| mesh[21].is_major_topic | True |
| mesh[21].qualifier_name | genetics |
| mesh[21].descriptor_name | BRCA2 Protein |
| mesh[22].qualifier_ui | Q000378 |
| mesh[22].descriptor_ui | D024682 |
| mesh[22].is_major_topic | True |
| mesh[22].qualifier_name | metabolism |
| mesh[22].descriptor_name | BRCA2 Protein |
| mesh[23].qualifier_ui | Q000494 |
| mesh[23].descriptor_ui | D010793 |
| mesh[23].is_major_topic | False |
| mesh[23].qualifier_name | pharmacology |
| mesh[23].descriptor_name | Phthalazines |
| mesh[24].qualifier_ui | |
| mesh[24].descriptor_ui | D006801 |
| mesh[24].is_major_topic | False |
| mesh[24].qualifier_name | |
| mesh[24].descriptor_name | Humans |
| mesh[25].qualifier_ui | Q000494 |
| mesh[25].descriptor_ui | D010879 |
| mesh[25].is_major_topic | False |
| mesh[25].qualifier_name | pharmacology |
| mesh[25].descriptor_name | Piperazines |
| mesh[26].qualifier_ui | |
| mesh[26].descriptor_ui | D009154 |
| mesh[26].is_major_topic | False |
| mesh[26].qualifier_name | |
| mesh[26].descriptor_name | Mutation |
| mesh[27].qualifier_ui | Q000235 |
| mesh[27].descriptor_ui | D018797 |
| mesh[27].is_major_topic | False |
| mesh[27].qualifier_name | genetics |
| mesh[27].descriptor_name | Cell Cycle Proteins |
| mesh[28].qualifier_ui | Q000378 |
| mesh[28].descriptor_ui | D018797 |
| mesh[28].is_major_topic | False |
| mesh[28].qualifier_name | metabolism |
| mesh[28].descriptor_name | Cell Cycle Proteins |
| mesh[29].qualifier_ui | Q000187 |
| mesh[29].descriptor_ui | D004261 |
| mesh[29].is_major_topic | False |
| mesh[29].qualifier_name | drug effects |
| mesh[29].descriptor_name | DNA Replication |
| mesh[30].qualifier_ui | Q000235 |
| mesh[30].descriptor_ui | D064129 |
| mesh[30].is_major_topic | False |
| mesh[30].qualifier_name | genetics |
| mesh[30].descriptor_name | Prostatic Neoplasms, Castration-Resistant |
| mesh[31].qualifier_ui | Q000188 |
| mesh[31].descriptor_ui | D064129 |
| mesh[31].is_major_topic | False |
| mesh[31].qualifier_name | drug therapy |
| mesh[31].descriptor_name | Prostatic Neoplasms, Castration-Resistant |
| mesh[32].qualifier_ui | Q000494 |
| mesh[32].descriptor_ui | D000067856 |
| mesh[32].is_major_topic | True |
| mesh[32].qualifier_name | pharmacology |
| mesh[32].descriptor_name | Poly(ADP-ribose) Polymerase Inhibitors |
| mesh[33].qualifier_ui | |
| mesh[33].descriptor_ui | D000818 |
| mesh[33].is_major_topic | False |
| mesh[33].qualifier_name | |
| mesh[33].descriptor_name | Animals |
| mesh[34].qualifier_ui | |
| mesh[34].descriptor_ui | D008297 |
| mesh[34].is_major_topic | False |
| mesh[34].qualifier_name | |
| mesh[34].descriptor_name | Male |
| mesh[35].qualifier_ui | |
| mesh[35].descriptor_ui | D051379 |
| mesh[35].is_major_topic | False |
| mesh[35].qualifier_name | |
| mesh[35].descriptor_name | Mice |
| mesh[36].qualifier_ui | Q000235 |
| mesh[36].descriptor_ui | D019008 |
| mesh[36].is_major_topic | True |
| mesh[36].qualifier_name | genetics |
| mesh[36].descriptor_name | Drug Resistance, Neoplasm |
| mesh[37].qualifier_ui | Q000235 |
| mesh[37].descriptor_ui | D024682 |
| mesh[37].is_major_topic | True |
| mesh[37].qualifier_name | genetics |
| mesh[37].descriptor_name | BRCA2 Protein |
| mesh[38].qualifier_ui | Q000378 |
| mesh[38].descriptor_ui | D024682 |
| mesh[38].is_major_topic | True |
| mesh[38].qualifier_name | metabolism |
| mesh[38].descriptor_name | BRCA2 Protein |
| mesh[39].qualifier_ui | Q000494 |
| mesh[39].descriptor_ui | D010793 |
| mesh[39].is_major_topic | False |
| mesh[39].qualifier_name | pharmacology |
| mesh[39].descriptor_name | Phthalazines |
| mesh[40].qualifier_ui | |
| mesh[40].descriptor_ui | D006801 |
| mesh[40].is_major_topic | False |
| mesh[40].qualifier_name | |
| mesh[40].descriptor_name | Humans |
| mesh[41].qualifier_ui | Q000494 |
| mesh[41].descriptor_ui | D010879 |
| mesh[41].is_major_topic | False |
| mesh[41].qualifier_name | pharmacology |
| mesh[41].descriptor_name | Piperazines |
| mesh[42].qualifier_ui | |
| mesh[42].descriptor_ui | D009154 |
| mesh[42].is_major_topic | False |
| mesh[42].qualifier_name | |
| mesh[42].descriptor_name | Mutation |
| mesh[43].qualifier_ui | Q000235 |
| mesh[43].descriptor_ui | D018797 |
| mesh[43].is_major_topic | False |
| mesh[43].qualifier_name | genetics |
| mesh[43].descriptor_name | Cell Cycle Proteins |
| mesh[44].qualifier_ui | Q000378 |
| mesh[44].descriptor_ui | D018797 |
| mesh[44].is_major_topic | False |
| mesh[44].qualifier_name | metabolism |
| mesh[44].descriptor_name | Cell Cycle Proteins |
| mesh[45].qualifier_ui | Q000187 |
| mesh[45].descriptor_ui | D004261 |
| mesh[45].is_major_topic | False |
| mesh[45].qualifier_name | drug effects |
| mesh[45].descriptor_name | DNA Replication |
| mesh[46].qualifier_ui | Q000235 |
| mesh[46].descriptor_ui | D064129 |
| mesh[46].is_major_topic | False |
| mesh[46].qualifier_name | genetics |
| mesh[46].descriptor_name | Prostatic Neoplasms, Castration-Resistant |
| mesh[47].qualifier_ui | Q000188 |
| mesh[47].descriptor_ui | D064129 |
| mesh[47].is_major_topic | False |
| mesh[47].qualifier_name | drug therapy |
| mesh[47].descriptor_name | Prostatic Neoplasms, Castration-Resistant |
| mesh[48].qualifier_ui | Q000494 |
| mesh[48].descriptor_ui | D000067856 |
| mesh[48].is_major_topic | True |
| mesh[48].qualifier_name | pharmacology |
| mesh[48].descriptor_name | Poly(ADP-ribose) Polymerase Inhibitors |
| mesh[49].qualifier_ui | |
| mesh[49].descriptor_ui | D000818 |
| mesh[49].is_major_topic | False |
| mesh[49].qualifier_name | |
| mesh[49].descriptor_name | Animals |
| type | article |
| title | BRCA2 reversion mutation–independent resistance to PARP inhibition through impaired DNA prereplication complex function |
| awards[0].id | https://openalex.org/G6838410686 |
| awards[0].funder_id | https://openalex.org/F4320306082 |
| awards[0].display_name | |
| awards[0].funder_award_id | not relevant |
| awards[0].funder_display_name | Howard Hughes Medical Institute |
| awards[1].id | https://openalex.org/G6238551472 |
| awards[1].funder_id | https://openalex.org/F4320332161 |
| awards[1].display_name | |
| awards[1].funder_award_id | 5F32CA236126-03 |
| awards[1].funder_display_name | National Institutes of Health |
| biblio.issue | 23 |
| biblio.volume | 122 |
| biblio.last_page | e2426743122 |
| biblio.first_page | e2426743122 |
| grants[0].funder | https://openalex.org/F4320306082 |
| grants[0].award_id | not relevant |
| grants[0].funder_display_name | Howard Hughes Medical Institute |
| grants[1].funder | https://openalex.org/F4320332161 |
| grants[1].award_id | 5F32CA236126-03 |
| grants[1].funder_display_name | National Institutes of Health |
| topics[0].id | https://openalex.org/T11914 |
| topics[0].field.id | https://openalex.org/fields/27 |
| topics[0].field.display_name | Medicine |
| topics[0].score | 0.9990000128746033 |
| topics[0].domain.id | https://openalex.org/domains/4 |
| topics[0].domain.display_name | Health Sciences |
| topics[0].subfield.id | https://openalex.org/subfields/2730 |
| topics[0].subfield.display_name | Oncology |
| topics[0].display_name | PARP inhibition in cancer therapy |
| topics[1].id | https://openalex.org/T10123 |
| topics[1].field.id | https://openalex.org/fields/13 |
| topics[1].field.display_name | Biochemistry, Genetics and Molecular Biology |
| topics[1].score | 0.9984999895095825 |
| topics[1].domain.id | https://openalex.org/domains/1 |
| topics[1].domain.display_name | Life Sciences |
| topics[1].subfield.id | https://openalex.org/subfields/1312 |
| topics[1].subfield.display_name | Molecular Biology |
| topics[1].display_name | DNA Repair Mechanisms |
| topics[2].id | https://openalex.org/T10878 |
| topics[2].field.id | https://openalex.org/fields/13 |
| topics[2].field.display_name | Biochemistry, Genetics and Molecular Biology |
| topics[2].score | 0.9955999851226807 |
| topics[2].domain.id | https://openalex.org/domains/1 |
| topics[2].domain.display_name | Life Sciences |
| topics[2].subfield.id | https://openalex.org/subfields/1312 |
| topics[2].subfield.display_name | Molecular Biology |
| topics[2].display_name | CRISPR and Genetic Engineering |
| funders[0].id | https://openalex.org/F4320306082 |
| funders[0].ror | https://ror.org/006w34k90 |
| funders[0].display_name | Howard Hughes Medical Institute |
| funders[1].id | https://openalex.org/F4320332161 |
| funders[1].ror | https://ror.org/01cwqze88 |
| funders[1].display_name | National Institutes of Health |
| is_xpac | False |
| apc_list | |
| apc_paid | |
| concepts[0].id | https://openalex.org/C70883133 |
| concepts[0].level | 4 |
| concepts[0].score | 0.9383590221405029 |
| concepts[0].wikidata | https://www.wikidata.org/wiki/Q7318316 |
| concepts[0].display_name | Reversion |
| concepts[1].id | https://openalex.org/C501734568 |
| concepts[1].level | 3 |
| concepts[1].score | 0.598815381526947 |
| concepts[1].wikidata | https://www.wikidata.org/wiki/Q42918 |
| concepts[1].display_name | Mutation |
| concepts[2].id | https://openalex.org/C54355233 |
| concepts[2].level | 1 |
| concepts[2].score | 0.5006883144378662 |
| concepts[2].wikidata | https://www.wikidata.org/wiki/Q7162 |
| concepts[2].display_name | Genetics |
| concepts[3].id | https://openalex.org/C57473165 |
| concepts[3].level | 2 |
| concepts[3].score | 0.4797026813030243 |
| concepts[3].wikidata | https://www.wikidata.org/wiki/Q7315604 |
| concepts[3].display_name | Resistance (ecology) |
| concepts[4].id | https://openalex.org/C14036430 |
| concepts[4].level | 2 |
| concepts[4].score | 0.4189223051071167 |
| concepts[4].wikidata | https://www.wikidata.org/wiki/Q3736076 |
| concepts[4].display_name | Function (biology) |
| concepts[5].id | https://openalex.org/C182979987 |
| concepts[5].level | 4 |
| concepts[5].score | 0.41625407338142395 |
| concepts[5].wikidata | https://www.wikidata.org/wiki/Q3907241 |
| concepts[5].display_name | Poly ADP ribose polymerase |
| concepts[6].id | https://openalex.org/C552990157 |
| concepts[6].level | 2 |
| concepts[6].score | 0.3842063546180725 |
| concepts[6].wikidata | https://www.wikidata.org/wiki/Q7430 |
| concepts[6].display_name | DNA |
| concepts[7].id | https://openalex.org/C86803240 |
| concepts[7].level | 0 |
| concepts[7].score | 0.3720967173576355 |
| concepts[7].wikidata | https://www.wikidata.org/wiki/Q420 |
| concepts[7].display_name | Biology |
| concepts[8].id | https://openalex.org/C502942594 |
| concepts[8].level | 1 |
| concepts[8].score | 0.3694832921028137 |
| concepts[8].wikidata | https://www.wikidata.org/wiki/Q3421914 |
| concepts[8].display_name | Cancer research |
| concepts[9].id | https://openalex.org/C127716648 |
| concepts[9].level | 3 |
| concepts[9].score | 0.10365727543830872 |
| concepts[9].wikidata | https://www.wikidata.org/wiki/Q104053 |
| concepts[9].display_name | Phenotype |
| concepts[10].id | https://openalex.org/C104317684 |
| concepts[10].level | 2 |
| concepts[10].score | 0.08296096324920654 |
| concepts[10].wikidata | https://www.wikidata.org/wiki/Q7187 |
| concepts[10].display_name | Gene |
| concepts[11].id | https://openalex.org/C82381507 |
| concepts[11].level | 3 |
| concepts[11].score | 0.06624570488929749 |
| concepts[11].wikidata | https://www.wikidata.org/wiki/Q416878 |
| concepts[11].display_name | Polymerase |
| concepts[12].id | https://openalex.org/C18903297 |
| concepts[12].level | 1 |
| concepts[12].score | 0.0 |
| concepts[12].wikidata | https://www.wikidata.org/wiki/Q7150 |
| concepts[12].display_name | Ecology |
| keywords[0].id | https://openalex.org/keywords/reversion |
| keywords[0].score | 0.9383590221405029 |
| keywords[0].display_name | Reversion |
| keywords[1].id | https://openalex.org/keywords/mutation |
| keywords[1].score | 0.598815381526947 |
| keywords[1].display_name | Mutation |
| keywords[2].id | https://openalex.org/keywords/genetics |
| keywords[2].score | 0.5006883144378662 |
| keywords[2].display_name | Genetics |
| keywords[3].id | https://openalex.org/keywords/resistance |
| keywords[3].score | 0.4797026813030243 |
| keywords[3].display_name | Resistance (ecology) |
| keywords[4].id | https://openalex.org/keywords/function |
| keywords[4].score | 0.4189223051071167 |
| keywords[4].display_name | Function (biology) |
| keywords[5].id | https://openalex.org/keywords/poly-adp-ribose-polymerase |
| keywords[5].score | 0.41625407338142395 |
| keywords[5].display_name | Poly ADP ribose polymerase |
| keywords[6].id | https://openalex.org/keywords/dna |
| keywords[6].score | 0.3842063546180725 |
| keywords[6].display_name | DNA |
| keywords[7].id | https://openalex.org/keywords/biology |
| keywords[7].score | 0.3720967173576355 |
| keywords[7].display_name | Biology |
| keywords[8].id | https://openalex.org/keywords/cancer-research |
| keywords[8].score | 0.3694832921028137 |
| keywords[8].display_name | Cancer research |
| keywords[9].id | https://openalex.org/keywords/phenotype |
| keywords[9].score | 0.10365727543830872 |
| keywords[9].display_name | Phenotype |
| keywords[10].id | https://openalex.org/keywords/gene |
| keywords[10].score | 0.08296096324920654 |
| keywords[10].display_name | Gene |
| keywords[11].id | https://openalex.org/keywords/polymerase |
| keywords[11].score | 0.06624570488929749 |
| keywords[11].display_name | Polymerase |
| language | en |
| locations[0].id | doi:10.1073/pnas.2426743122 |
| locations[0].is_oa | True |
| locations[0].source.id | https://openalex.org/S125754415 |
| locations[0].source.issn | 0027-8424, 1091-6490 |
| locations[0].source.type | journal |
| locations[0].source.is_oa | False |
| locations[0].source.issn_l | 0027-8424 |
| locations[0].source.is_core | True |
| locations[0].source.is_in_doaj | False |
| locations[0].source.display_name | Proceedings of the National Academy of Sciences |
| locations[0].source.host_organization | https://openalex.org/P4310320052 |
| locations[0].source.host_organization_name | National Academy of Sciences |
| locations[0].source.host_organization_lineage | https://openalex.org/P4310320052 |
| locations[0].source.host_organization_lineage_names | National Academy of Sciences |
| locations[0].license | cc-by |
| locations[0].pdf_url | https://www.pnas.org/doi/pdf/10.1073/pnas.2426743122 |
| locations[0].version | publishedVersion |
| locations[0].raw_type | journal-article |
| locations[0].license_id | https://openalex.org/licenses/cc-by |
| locations[0].is_accepted | True |
| locations[0].is_published | True |
| locations[0].raw_source_name | Proceedings of the National Academy of Sciences |
| locations[0].landing_page_url | https://doi.org/10.1073/pnas.2426743122 |
| locations[1].id | pmh:oai:pubmedcentral.nih.gov:12167974 |
| locations[1].is_oa | True |
| locations[1].source.id | https://openalex.org/S2764455111 |
| locations[1].source.issn | |
| locations[1].source.type | repository |
| locations[1].source.is_oa | False |
| locations[1].source.issn_l | |
| locations[1].source.is_core | False |
| locations[1].source.is_in_doaj | False |
| locations[1].source.display_name | PubMed Central |
| locations[1].source.host_organization | https://openalex.org/I1299303238 |
| locations[1].source.host_organization_name | National Institutes of Health |
| locations[1].source.host_organization_lineage | https://openalex.org/I1299303238 |
| locations[1].license | other-oa |
| locations[1].pdf_url | |
| locations[1].version | publishedVersion |
| locations[1].raw_type | Text |
| locations[1].license_id | https://openalex.org/licenses/other-oa |
| locations[1].is_accepted | True |
| locations[1].is_published | True |
| locations[1].raw_source_name | Proc Natl Acad Sci U S A |
| locations[1].landing_page_url | https://www.ncbi.nlm.nih.gov/pmc/articles/12167974 |
| locations[2].id | pmid:40460119 |
| locations[2].is_oa | False |
| locations[2].source.id | https://openalex.org/S4306525036 |
| locations[2].source.issn | |
| locations[2].source.type | repository |
| locations[2].source.is_oa | False |
| locations[2].source.issn_l | |
| locations[2].source.is_core | False |
| locations[2].source.is_in_doaj | False |
| locations[2].source.display_name | PubMed |
| locations[2].source.host_organization | https://openalex.org/I1299303238 |
| locations[2].source.host_organization_name | National Institutes of Health |
| locations[2].source.host_organization_lineage | https://openalex.org/I1299303238 |
| locations[2].license | |
| locations[2].pdf_url | |
| locations[2].version | publishedVersion |
| locations[2].raw_type | |
| locations[2].license_id | |
| locations[2].is_accepted | True |
| locations[2].is_published | True |
| locations[2].raw_source_name | Proceedings of the National Academy of Sciences of the United States of America |
| locations[2].landing_page_url | https://pubmed.ncbi.nlm.nih.gov/40460119 |
| indexed_in | crossref, pubmed |
| authorships[0].author.id | https://openalex.org/A5081856669 |
| authorships[0].author.orcid | https://orcid.org/0000-0002-1828-246X |
| authorships[0].author.display_name | Kyrie Pappas |
| authorships[0].countries | US |
| authorships[0].affiliations[0].institution_ids | https://openalex.org/I1334819555 |
| authorships[0].affiliations[0].raw_affiliation_string | Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center |
| authorships[0].institutions[0].id | https://openalex.org/I1334819555 |
| authorships[0].institutions[0].ror | https://ror.org/02yrq0923 |
| authorships[0].institutions[0].type | healthcare |
| authorships[0].institutions[0].lineage | https://openalex.org/I1334819555 |
| authorships[0].institutions[0].country_code | US |
| authorships[0].institutions[0].display_name | Memorial Sloan Kettering Cancer Center |
| authorships[0].author_position | first |
| authorships[0].raw_author_name | Kyrie Pappas |
| authorships[0].is_corresponding | False |
| authorships[0].raw_affiliation_strings | Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center |
| authorships[1].author.id | https://openalex.org/A5101806620 |
| authorships[1].author.orcid | https://orcid.org/0000-0001-6672-3170 |
| authorships[1].author.display_name | Matteo Ferrari |
| authorships[1].countries | US |
| authorships[1].affiliations[0].institution_ids | https://openalex.org/I1334819555 |
| authorships[1].affiliations[0].raw_affiliation_string | Developmental Biology Program, Memorial Sloan Kettering Cancer Center |
| authorships[1].institutions[0].id | https://openalex.org/I1334819555 |
| authorships[1].institutions[0].ror | https://ror.org/02yrq0923 |
| authorships[1].institutions[0].type | healthcare |
| authorships[1].institutions[0].lineage | https://openalex.org/I1334819555 |
| authorships[1].institutions[0].country_code | US |
| authorships[1].institutions[0].display_name | Memorial Sloan Kettering Cancer Center |
| authorships[1].author_position | middle |
| authorships[1].raw_author_name | Matteo Ferrari |
| authorships[1].is_corresponding | False |
| authorships[1].raw_affiliation_strings | Developmental Biology Program, Memorial Sloan Kettering Cancer Center |
| authorships[2].author.id | https://openalex.org/A5067534462 |
| authorships[2].author.orcid | |
| authorships[2].author.display_name | Perianne Smith |
| authorships[2].countries | US |
| authorships[2].affiliations[0].institution_ids | https://openalex.org/I130238516 |
| authorships[2].affiliations[0].raw_affiliation_string | Department of Microbiology, Immunology, and Cancer Biology, University of Minnesota |
| authorships[2].institutions[0].id | https://openalex.org/I130238516 |
| authorships[2].institutions[0].ror | https://ror.org/017zqws13 |
| authorships[2].institutions[0].type | education |
| authorships[2].institutions[0].lineage | https://openalex.org/I130238516 |
| authorships[2].institutions[0].country_code | US |
| authorships[2].institutions[0].display_name | University of Minnesota |
| authorships[2].author_position | middle |
| authorships[2].raw_author_name | Perianne Smith |
| authorships[2].is_corresponding | False |
| authorships[2].raw_affiliation_strings | Department of Microbiology, Immunology, and Cancer Biology, University of Minnesota |
| authorships[3].author.id | https://openalex.org/A5080705644 |
| authorships[3].author.orcid | https://orcid.org/0000-0003-0258-3484 |
| authorships[3].author.display_name | Subhiksha Nandakumar |
| authorships[3].countries | US |
| authorships[3].affiliations[0].institution_ids | https://openalex.org/I1334819555 |
| authorships[3].affiliations[0].raw_affiliation_string | The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center |
| authorships[3].affiliations[1].institution_ids | https://openalex.org/I1334819555 |
| authorships[3].affiliations[1].raw_affiliation_string | Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center |
| authorships[3].institutions[0].id | https://openalex.org/I1334819555 |
| authorships[3].institutions[0].ror | https://ror.org/02yrq0923 |
| authorships[3].institutions[0].type | healthcare |
| authorships[3].institutions[0].lineage | https://openalex.org/I1334819555 |
| authorships[3].institutions[0].country_code | US |
| authorships[3].institutions[0].display_name | Memorial Sloan Kettering Cancer Center |
| authorships[3].author_position | middle |
| authorships[3].raw_author_name | Subhiksha Nandakumar |
| authorships[3].is_corresponding | False |
| authorships[3].raw_affiliation_strings | Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center |
| authorships[4].author.id | https://openalex.org/A5081416491 |
| authorships[4].author.orcid | |
| authorships[4].author.display_name | Zahra Khan |
| authorships[4].countries | US |
| authorships[4].affiliations[0].institution_ids | https://openalex.org/I1334819555 |
| authorships[4].affiliations[0].raw_affiliation_string | Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center |
| authorships[4].institutions[0].id | https://openalex.org/I1334819555 |
| authorships[4].institutions[0].ror | https://ror.org/02yrq0923 |
| authorships[4].institutions[0].type | healthcare |
| authorships[4].institutions[0].lineage | https://openalex.org/I1334819555 |
| authorships[4].institutions[0].country_code | US |
| authorships[4].institutions[0].display_name | Memorial Sloan Kettering Cancer Center |
| authorships[4].author_position | middle |
| authorships[4].raw_author_name | Zahra Khan |
| authorships[4].is_corresponding | False |
| authorships[4].raw_affiliation_strings | Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center |
| authorships[5].author.id | https://openalex.org/A5011998094 |
| authorships[5].author.orcid | |
| authorships[5].author.display_name | Serina B. Young |
| authorships[5].countries | US |
| authorships[5].affiliations[0].institution_ids | https://openalex.org/I2799503643 |
| authorships[5].affiliations[0].raw_affiliation_string | Department of Neurosurgery, Columbia University Irving Medical Center |
| authorships[5].institutions[0].id | https://openalex.org/I2799503643 |
| authorships[5].institutions[0].ror | https://ror.org/01esghr10 |
| authorships[5].institutions[0].type | healthcare |
| authorships[5].institutions[0].lineage | https://openalex.org/I2799503643 |
| authorships[5].institutions[0].country_code | US |
| authorships[5].institutions[0].display_name | Columbia University Irving Medical Center |
| authorships[5].author_position | middle |
| authorships[5].raw_author_name | Serina B. Young |
| authorships[5].is_corresponding | False |
| authorships[5].raw_affiliation_strings | Department of Neurosurgery, Columbia University Irving Medical Center |
| authorships[6].author.id | https://openalex.org/A5013859888 |
| authorships[6].author.orcid | |
| authorships[6].author.display_name | Justin LaClair |
| authorships[6].countries | US |
| authorships[6].affiliations[0].institution_ids | https://openalex.org/I77920804 |
| authorships[6].affiliations[0].raw_affiliation_string | Albany Medical College |
| authorships[6].institutions[0].id | https://openalex.org/I77920804 |
| authorships[6].institutions[0].ror | https://ror.org/0307crw42 |
| authorships[6].institutions[0].type | healthcare |
| authorships[6].institutions[0].lineage | https://openalex.org/I77920804 |
| authorships[6].institutions[0].country_code | US |
| authorships[6].institutions[0].display_name | Albany Medical Center Hospital |
| authorships[6].author_position | middle |
| authorships[6].raw_author_name | Justin LaClair |
| authorships[6].is_corresponding | False |
| authorships[6].raw_affiliation_strings | Albany Medical College |
| authorships[7].author.id | https://openalex.org/A5029988051 |
| authorships[7].author.orcid | https://orcid.org/0000-0002-5148-1305 |
| authorships[7].author.display_name | Marco Vincenzo Russo |
| authorships[7].countries | US |
| authorships[7].affiliations[0].institution_ids | https://openalex.org/I145608581, https://openalex.org/I4210157065 |
| authorships[7].affiliations[0].raw_affiliation_string | Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami |
| authorships[7].institutions[0].id | https://openalex.org/I4210157065 |
| authorships[7].institutions[0].ror | https://ror.org/0552r4b12 |
| authorships[7].institutions[0].type | healthcare |
| authorships[7].institutions[0].lineage | https://openalex.org/I145608581, https://openalex.org/I4210101935, https://openalex.org/I4210157065 |
| authorships[7].institutions[0].country_code | US |
| authorships[7].institutions[0].display_name | Sylvester Comprehensive Cancer Center |
| authorships[7].institutions[1].id | https://openalex.org/I145608581 |
| authorships[7].institutions[1].ror | https://ror.org/02dgjyy92 |
| authorships[7].institutions[1].type | education |
| authorships[7].institutions[1].lineage | https://openalex.org/I145608581 |
| authorships[7].institutions[1].country_code | US |
| authorships[7].institutions[1].display_name | University of Miami |
| authorships[7].author_position | middle |
| authorships[7].raw_author_name | Marco Vincenzo Russo |
| authorships[7].is_corresponding | False |
| authorships[7].raw_affiliation_strings | Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami |
| authorships[8].author.id | https://openalex.org/A5062328180 |
| authorships[8].author.orcid | https://orcid.org/0000-0002-2071-2588 |
| authorships[8].author.display_name | Emmet Huang-Hobbs |
| authorships[8].countries | US |
| authorships[8].affiliations[0].institution_ids | https://openalex.org/I1334819555 |
| authorships[8].affiliations[0].raw_affiliation_string | Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center |
| authorships[8].institutions[0].id | https://openalex.org/I1334819555 |
| authorships[8].institutions[0].ror | https://ror.org/02yrq0923 |
| authorships[8].institutions[0].type | healthcare |
| authorships[8].institutions[0].lineage | https://openalex.org/I1334819555 |
| authorships[8].institutions[0].country_code | US |
| authorships[8].institutions[0].display_name | Memorial Sloan Kettering Cancer Center |
| authorships[8].author_position | middle |
| authorships[8].raw_author_name | Emmet Huang-Hobbs |
| authorships[8].is_corresponding | False |
| authorships[8].raw_affiliation_strings | Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center |
| authorships[9].author.id | https://openalex.org/A5033125884 |
| authorships[9].author.orcid | https://orcid.org/0000-0002-0131-4904 |
| authorships[9].author.display_name | Nikolaus Schultz |
| authorships[9].countries | US |
| authorships[9].affiliations[0].institution_ids | https://openalex.org/I1334819555 |
| authorships[9].affiliations[0].raw_affiliation_string | The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center |
| authorships[9].affiliations[1].institution_ids | https://openalex.org/I1334819555 |
| authorships[9].affiliations[1].raw_affiliation_string | Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center |
| authorships[9].affiliations[2].institution_ids | https://openalex.org/I1334819555 |
| authorships[9].affiliations[2].raw_affiliation_string | Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center |
| authorships[9].institutions[0].id | https://openalex.org/I1334819555 |
| authorships[9].institutions[0].ror | https://ror.org/02yrq0923 |
| authorships[9].institutions[0].type | healthcare |
| authorships[9].institutions[0].lineage | https://openalex.org/I1334819555 |
| authorships[9].institutions[0].country_code | US |
| authorships[9].institutions[0].display_name | Memorial Sloan Kettering Cancer Center |
| authorships[9].author_position | middle |
| authorships[9].raw_author_name | Nikolaus Schultz |
| authorships[9].is_corresponding | False |
| authorships[9].raw_affiliation_strings | Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center |
| authorships[10].author.id | https://openalex.org/A5062426672 |
| authorships[10].author.orcid | https://orcid.org/0000-0002-9006-7043 |
| authorships[10].author.display_name | Wassim Abida |
| authorships[10].countries | US |
| authorships[10].affiliations[0].institution_ids | https://openalex.org/I1334819555 |
| authorships[10].affiliations[0].raw_affiliation_string | Department of Medicine, Memorial Sloan Kettering Cancer Center |
| authorships[10].institutions[0].id | https://openalex.org/I1334819555 |
| authorships[10].institutions[0].ror | https://ror.org/02yrq0923 |
| authorships[10].institutions[0].type | healthcare |
| authorships[10].institutions[0].lineage | https://openalex.org/I1334819555 |
| authorships[10].institutions[0].country_code | US |
| authorships[10].institutions[0].display_name | Memorial Sloan Kettering Cancer Center |
| authorships[10].author_position | middle |
| authorships[10].raw_author_name | Wassim Abida |
| authorships[10].is_corresponding | False |
| authorships[10].raw_affiliation_strings | Department of Medicine, Memorial Sloan Kettering Cancer Center |
| authorships[11].author.id | https://openalex.org/A5009209065 |
| authorships[11].author.orcid | https://orcid.org/0000-0002-9234-9044 |
| authorships[11].author.display_name | Wouter R. Karthaus |
| authorships[11].countries | CH |
| authorships[11].affiliations[0].institution_ids | https://openalex.org/I5124864 |
| authorships[11].affiliations[0].raw_affiliation_string | Swiss Institute for Experimental Cancer Research, The École Polytechnique Fédérale de Lausanne |
| authorships[11].institutions[0].id | https://openalex.org/I5124864 |
| authorships[11].institutions[0].ror | https://ror.org/02s376052 |
| authorships[11].institutions[0].type | education |
| authorships[11].institutions[0].lineage | https://openalex.org/I2799323385, https://openalex.org/I5124864 |
| authorships[11].institutions[0].country_code | CH |
| authorships[11].institutions[0].display_name | École Polytechnique Fédérale de Lausanne |
| authorships[11].author_position | middle |
| authorships[11].raw_author_name | Wouter Karthaus |
| authorships[11].is_corresponding | False |
| authorships[11].raw_affiliation_strings | Swiss Institute for Experimental Cancer Research, The École Polytechnique Fédérale de Lausanne |
| authorships[12].author.id | https://openalex.org/A5089227056 |
| authorships[12].author.orcid | https://orcid.org/0000-0002-7976-2379 |
| authorships[12].author.display_name | Maria Jasin |
| authorships[12].countries | US |
| authorships[12].affiliations[0].institution_ids | https://openalex.org/I1334819555 |
| authorships[12].affiliations[0].raw_affiliation_string | Developmental Biology Program, Memorial Sloan Kettering Cancer Center |
| authorships[12].institutions[0].id | https://openalex.org/I1334819555 |
| authorships[12].institutions[0].ror | https://ror.org/02yrq0923 |
| authorships[12].institutions[0].type | healthcare |
| authorships[12].institutions[0].lineage | https://openalex.org/I1334819555 |
| authorships[12].institutions[0].country_code | US |
| authorships[12].institutions[0].display_name | Memorial Sloan Kettering Cancer Center |
| authorships[12].author_position | middle |
| authorships[12].raw_author_name | Maria Jasin |
| authorships[12].is_corresponding | False |
| authorships[12].raw_affiliation_strings | Developmental Biology Program, Memorial Sloan Kettering Cancer Center |
| authorships[13].author.id | https://openalex.org/A5034963668 |
| authorships[13].author.orcid | https://orcid.org/0000-0003-4955-6475 |
| authorships[13].author.display_name | Charles L. Sawyers |
| authorships[13].countries | US |
| authorships[13].affiliations[0].institution_ids | https://openalex.org/I1334819555 |
| authorships[13].affiliations[0].raw_affiliation_string | Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center |
| authorships[13].institutions[0].id | https://openalex.org/I1334819555 |
| authorships[13].institutions[0].ror | https://ror.org/02yrq0923 |
| authorships[13].institutions[0].type | healthcare |
| authorships[13].institutions[0].lineage | https://openalex.org/I1334819555 |
| authorships[13].institutions[0].country_code | US |
| authorships[13].institutions[0].display_name | Memorial Sloan Kettering Cancer Center |
| authorships[13].author_position | last |
| authorships[13].raw_author_name | Charles L. Sawyers |
| authorships[13].is_corresponding | False |
| authorships[13].raw_affiliation_strings | Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center |
| has_content.pdf | True |
| has_content.grobid_xml | True |
| is_paratext | False |
| open_access.is_oa | True |
| open_access.oa_url | https://www.pnas.org/doi/pdf/10.1073/pnas.2426743122 |
| open_access.oa_status | hybrid |
| open_access.any_repository_has_fulltext | False |
| created_date | 2025-10-10T00:00:00 |
| display_name | BRCA2 reversion mutation–independent resistance to PARP inhibition through impaired DNA prereplication complex function |
| has_fulltext | True |
| is_retracted | False |
| updated_date | 2025-11-06T03:46:38.306776 |
| primary_topic.id | https://openalex.org/T11914 |
| primary_topic.field.id | https://openalex.org/fields/27 |
| primary_topic.field.display_name | Medicine |
| primary_topic.score | 0.9990000128746033 |
| primary_topic.domain.id | https://openalex.org/domains/4 |
| primary_topic.domain.display_name | Health Sciences |
| primary_topic.subfield.id | https://openalex.org/subfields/2730 |
| primary_topic.subfield.display_name | Oncology |
| primary_topic.display_name | PARP inhibition in cancer therapy |
| related_works | https://openalex.org/W2033210022, https://openalex.org/W2093399047, https://openalex.org/W2385182213, https://openalex.org/W2071006786, https://openalex.org/W2075853330, https://openalex.org/W2075245653, https://openalex.org/W2415523191, https://openalex.org/W4210930028, https://openalex.org/W2036303296, https://openalex.org/W2004386997 |
| cited_by_count | 2 |
| counts_by_year[0].year | 2025 |
| counts_by_year[0].cited_by_count | 2 |
| locations_count | 3 |
| best_oa_location.id | doi:10.1073/pnas.2426743122 |
| best_oa_location.is_oa | True |
| best_oa_location.source.id | https://openalex.org/S125754415 |
| best_oa_location.source.issn | 0027-8424, 1091-6490 |
| best_oa_location.source.type | journal |
| best_oa_location.source.is_oa | False |
| best_oa_location.source.issn_l | 0027-8424 |
| best_oa_location.source.is_core | True |
| best_oa_location.source.is_in_doaj | False |
| best_oa_location.source.display_name | Proceedings of the National Academy of Sciences |
| best_oa_location.source.host_organization | https://openalex.org/P4310320052 |
| best_oa_location.source.host_organization_name | National Academy of Sciences |
| best_oa_location.source.host_organization_lineage | https://openalex.org/P4310320052 |
| best_oa_location.source.host_organization_lineage_names | National Academy of Sciences |
| best_oa_location.license | cc-by |
| best_oa_location.pdf_url | https://www.pnas.org/doi/pdf/10.1073/pnas.2426743122 |
| best_oa_location.version | publishedVersion |
| best_oa_location.raw_type | journal-article |
| best_oa_location.license_id | https://openalex.org/licenses/cc-by |
| best_oa_location.is_accepted | True |
| best_oa_location.is_published | True |
| best_oa_location.raw_source_name | Proceedings of the National Academy of Sciences |
| best_oa_location.landing_page_url | https://doi.org/10.1073/pnas.2426743122 |
| primary_location.id | doi:10.1073/pnas.2426743122 |
| primary_location.is_oa | True |
| primary_location.source.id | https://openalex.org/S125754415 |
| primary_location.source.issn | 0027-8424, 1091-6490 |
| primary_location.source.type | journal |
| primary_location.source.is_oa | False |
| primary_location.source.issn_l | 0027-8424 |
| primary_location.source.is_core | True |
| primary_location.source.is_in_doaj | False |
| primary_location.source.display_name | Proceedings of the National Academy of Sciences |
| primary_location.source.host_organization | https://openalex.org/P4310320052 |
| primary_location.source.host_organization_name | National Academy of Sciences |
| primary_location.source.host_organization_lineage | https://openalex.org/P4310320052 |
| primary_location.source.host_organization_lineage_names | National Academy of Sciences |
| primary_location.license | cc-by |
| primary_location.pdf_url | https://www.pnas.org/doi/pdf/10.1073/pnas.2426743122 |
| primary_location.version | publishedVersion |
| primary_location.raw_type | journal-article |
| primary_location.license_id | https://openalex.org/licenses/cc-by |
| primary_location.is_accepted | True |
| primary_location.is_published | True |
| primary_location.raw_source_name | Proceedings of the National Academy of Sciences |
| primary_location.landing_page_url | https://doi.org/10.1073/pnas.2426743122 |
| publication_date | 2025-06-03 |
| publication_year | 2025 |
| referenced_works | https://openalex.org/W2991669855, https://openalex.org/W3049351332, https://openalex.org/W3014088197, https://openalex.org/W2732346161, https://openalex.org/W2009007206, https://openalex.org/W1973268287, https://openalex.org/W2888002479, https://openalex.org/W1531540594, https://openalex.org/W2900633622, https://openalex.org/W4391100936, https://openalex.org/W2767593721, https://openalex.org/W2972243271, https://openalex.org/W3204453900, https://openalex.org/W4401881938, https://openalex.org/W4404588077, https://openalex.org/W4304891591, https://openalex.org/W2058957446, https://openalex.org/W2808113406, https://openalex.org/W2476568892, https://openalex.org/W2156500939, https://openalex.org/W2762278714, https://openalex.org/W2883789961, https://openalex.org/W4316804884, https://openalex.org/W4290034386, https://openalex.org/W4399301349, https://openalex.org/W2900491285, https://openalex.org/W4402530070, https://openalex.org/W2006001375, https://openalex.org/W3192622360, https://openalex.org/W4403338465, https://openalex.org/W2316393988, https://openalex.org/W2255555283, https://openalex.org/W2252568502, https://openalex.org/W4386438154, https://openalex.org/W2149441684, https://openalex.org/W3094213757, https://openalex.org/W1979481942, https://openalex.org/W2149792163, https://openalex.org/W4224861452, https://openalex.org/W2982214814, https://openalex.org/W2031211461, https://openalex.org/W2470801200 |
| referenced_works_count | 42 |
| abstract_inverted_index.( | 115 |
| abstract_inverted_index.) | 120 |
| abstract_inverted_index., | 152 |
| abstract_inverted_index.. | 193 |
| abstract_inverted_index.a | 73, 93, 160, 171, 246, 260 |
| abstract_inverted_index.HR | 242 |
| abstract_inverted_index.Of | 244 |
| abstract_inverted_index.To | 67 |
| abstract_inverted_index.an | 19 |
| abstract_inverted_index.as | 208, 210 |
| abstract_inverted_index.by | 156, 217, 235 |
| abstract_inverted_index.in | 39, 84, 92, 149, 175, 238 |
| abstract_inverted_index.is | 53 |
| abstract_inverted_index.of | 2, 21, 43, 61, 81, 99, 121, 128, 158, 163, 170, 180, 187, 204, 241 |
| abstract_inverted_index.to | 41, 77, 133, 144, 257, 264, 267 |
| abstract_inverted_index.we | 71, 103 |
| abstract_inverted_index.80% | 42 |
| abstract_inverted_index.DNA | 123, 206 |
| abstract_inverted_index.and | 27, 118, 135 |
| abstract_inverted_index.are | 37 |
| abstract_inverted_index.but | 48, 51 |
| abstract_inverted_index.can | 227 |
| abstract_inverted_index.for | 11 |
| abstract_inverted_index.how | 223 |
| abstract_inverted_index.the | 22, 97, 122, 136, 167, 239, 251 |
| abstract_inverted_index.was | 147 |
| abstract_inverted_index.who | 46 |
| abstract_inverted_index.why | 58 |
| abstract_inverted_index.~50 | 40 |
| abstract_inverted_index.(HR) | 35 |
| abstract_inverted_index.CDT1 | 192 |
| abstract_inverted_index.CRPC | 181 |
| abstract_inverted_index.Dbf4 | 119 |
| abstract_inverted_index.PARP | 145, 236, 268 |
| abstract_inverted_index.RNAs | 109 |
| abstract_inverted_index.cell | 229 |
| abstract_inverted_index.copy | 184 |
| abstract_inverted_index.each | 127 |
| abstract_inverted_index.fork | 214 |
| abstract_inverted_index.from | 212, 231 |
| abstract_inverted_index.have | 183 |
| abstract_inverted_index.into | 57, 222 |
| abstract_inverted_index.loss | 186 |
| abstract_inverted_index.only | 59 |
| abstract_inverted_index.role | 169 |
| abstract_inverted_index.that | 24, 31, 95, 249 |
| abstract_inverted_index.this | 69 |
| abstract_inverted_index.well | 209 |
| abstract_inverted_index.with | 197 |
| abstract_inverted_index.~50% | 60, 179 |
| abstract_inverted_index.Brca2 | 86, 150, 218 |
| abstract_inverted_index.Cdc6, | 117 |
| abstract_inverted_index.Cdt1, | 116, 164 |
| abstract_inverted_index.PARPi | 82, 176 |
| abstract_inverted_index.cells | 155, 196, 226 |
| abstract_inverted_index.death | 230 |
| abstract_inverted_index.guide | 108 |
| abstract_inverted_index.loss, | 219 |
| abstract_inverted_index.note, | 245 |
| abstract_inverted_index.rapid | 202 |
| abstract_inverted_index.shape | 25 |
| abstract_inverted_index.there | 52 |
| abstract_inverted_index.three | 112 |
| abstract_inverted_index.which | 129 |
| abstract_inverted_index.Δ/Δ | 87, 151 |
| abstract_inverted_index.CRISPR | 75 |
| abstract_inverted_index.PARP-1 | 138 |
| abstract_inverted_index.Recent | 0 |
| abstract_inverted_index.avenue | 263 |
| abstract_inverted_index.cancer | 17, 225 |
| abstract_inverted_index.caused | 216 |
| abstract_inverted_index.damage | 207 |
| abstract_inverted_index.escape | 228 |
| abstract_inverted_index.genes, | 190 |
| abstract_inverted_index.little | 55 |
| abstract_inverted_index.manner | 94 |
| abstract_inverted_index.murine | 85 |
| abstract_inverted_index.number | 185 |
| abstract_inverted_index.pre-RC | 173, 188, 199 |
| abstract_inverted_index.repair | 36 |
| abstract_inverted_index.ribose | 6 |
| abstract_inverted_index.screen | 76 |
| abstract_inverted_index.single | 107 |
| abstract_inverted_index.stress | 233 |
| abstract_inverted_index.tumors | 182 |
| abstract_inverted_index.(AF615) | 254 |
| abstract_inverted_index.(PARPi) | 10 |
| abstract_inverted_index.absence | 240 |
| abstract_inverted_index.address | 68 |
| abstract_inverted_index.complex | 125, 174, 189, 253 |
| abstract_inverted_index.display | 64 |
| abstract_inverted_index.enhance | 265 |
| abstract_inverted_index.factors | 23 |
| abstract_inverted_index.further | 165 |
| abstract_inverted_index.genomic | 79 |
| abstract_inverted_index.induced | 234 |
| abstract_inverted_index.insight | 56, 221 |
| abstract_inverted_index.members | 114 |
| abstract_inverted_index.repair. | 243 |
| abstract_inverted_index.respond | 47 |
| abstract_inverted_index.restore | 32 |
| abstract_inverted_index.targets | 250 |
| abstract_inverted_index.upfront | 65 |
| abstract_inverted_index.(sgRNAs) | 110 |
| abstract_inverted_index.AZD5305, | 258 |
| abstract_inverted_index.AZD5305. | 141 |
| abstract_inverted_index.activity | 200 |
| abstract_inverted_index.critical | 168 |
| abstract_inverted_index.detected | 38 |
| abstract_inverted_index.geminin, | 159 |
| abstract_inverted_index.identify | 78 |
| abstract_inverted_index.impaired | 198 |
| abstract_inverted_index.multiple | 105 |
| abstract_inverted_index.negative | 161 |
| abstract_inverted_index.olaparib | 134 |
| abstract_inverted_index.patients | 45, 63 |
| abstract_inverted_index.prostate | 16, 88, 154, 195 |
| abstract_inverted_index.relapse, | 50 |
| abstract_inverted_index.restored | 148, 255 |
| abstract_inverted_index.(pre-RC), | 126 |
| abstract_inverted_index.Moreover, | 142 |
| abstract_inverted_index.Reversion | 29 |
| abstract_inverted_index.adenosine | 4 |
| abstract_inverted_index.approvals | 1 |
| abstract_inverted_index.conferred | 131 |
| abstract_inverted_index.currently | 54 |
| abstract_inverted_index.different | 113 |
| abstract_inverted_index.displayed | 201 |
| abstract_inverted_index.inhibitor | 140, 248 |
| abstract_inverted_index.knockdown | 157 |
| abstract_inverted_index.mutations | 30 |
| abstract_inverted_index.organoids | 89 |
| abstract_inverted_index.performed | 72 |
| abstract_inverted_index.polymeric | 3 |
| abstract_inverted_index.potential | 261 |
| abstract_inverted_index.precludes | 96 |
| abstract_inverted_index.providing | 220, 259 |
| abstract_inverted_index.question, | 70 |
| abstract_inverted_index.recovered | 104 |
| abstract_inverted_index.regulator | 162 |
| abstract_inverted_index.resistant | 15 |
| abstract_inverted_index.reversion | 100 |
| abstract_inverted_index.selective | 139 |
| abstract_inverted_index.targeting | 111 |
| abstract_inverted_index.castration | 14 |
| abstract_inverted_index.engineered | 91 |
| abstract_inverted_index.functional | 172 |
| abstract_inverted_index.homologous | 33 |
| abstract_inverted_index.inhibition | 146, 237 |
| abstract_inverted_index.inhibitors | 9 |
| abstract_inverted_index.metastatic | 13 |
| abstract_inverted_index.mutations. | 101 |
| abstract_inverted_index.polymerase | 8 |
| abstract_inverted_index.protection | 211 |
| abstract_inverted_index.resistance | 83, 132 |
| abstract_inverted_index.resolution | 203 |
| abstract_inverted_index.BRCA-mutant | 12, 44, 62 |
| abstract_inverted_index.Remarkably, | 102 |
| abstract_inverted_index.degradation | 215 |
| abstract_inverted_index.development | 98 |
| abstract_inverted_index.diphosphate | 5 |
| abstract_inverted_index.genetically | 90 |
| abstract_inverted_index.genome-wide | 74 |
| abstract_inverted_index.implicating | 166 |
| abstract_inverted_index.independent | 106 |
| abstract_inverted_index.inhibition. | 269 |
| abstract_inverted_index.necessitate | 18 |
| abstract_inverted_index.replication | 213, 232 |
| abstract_inverted_index.resistance. | 28, 66 |
| abstract_inverted_index.sensitivity | 26, 143, 256, 266 |
| abstract_inverted_index.Brca2-mutant | 224 |
| abstract_inverted_index.CDT1/geminin | 252 |
| abstract_inverted_index.Furthermore, | 178 |
| abstract_inverted_index.determinants | 80 |
| abstract_inverted_index.particularly | 191 |
| abstract_inverted_index.sensitivity. | 177 |
| abstract_inverted_index.subsequently | 49 |
| abstract_inverted_index.Cdc6-depleted | 153 |
| abstract_inverted_index.independently | 130 |
| abstract_inverted_index.pharmacologic | 247 |
| abstract_inverted_index.recombination | 34 |
| abstract_inverted_index.translational | 262 |
| abstract_inverted_index.understanding | 20 |
| abstract_inverted_index.prereplication | 124 |
| abstract_inverted_index.next-generation | 137 |
| abstract_inverted_index.Mechanistically, | 194 |
| abstract_inverted_index.olaparib-induced | 205 |
| abstract_inverted_index.(poly(ADP-ribose) | 7 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 95 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 14 |
| citation_normalized_percentile.value | 0.92941542 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |