PCAF promotes R-loop resolution via histone acetylation Article Swipe
Seo Yun Lee
,
Soo Hyun Lee
,
Nak Hun Choi
,
Ja Young Kim
,
Jun Hee Kweon
,
Kyle M. Miller
,
Jae Jin Kim
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1093/nar/gkae558
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1093/nar/gkae558
R-loops cause genome instability, disrupting normal cellular functions. Histone acetylation, particularly by p300/CBP-associated factor (PCAF), is essential for maintaining genome stability and regulating cellular processes. Understanding how R-loop formation and resolution are regulated is important because dysregulation of these processes can lead to multiple diseases, including cancer. This study explores the role of PCAF in maintaining genome stability, specifically for R-loop resolution. We found that PCAF depletion promotes the generation of R-loop structures, especially during ongoing transcription, thereby compromising genome stability. Mechanistically, we found that PCAF facilitates histone H4K8 acetylation, leading to recruitment of the a double-strand break repair protein (MRE11) and exonuclease 1 (EXO1) to R-loop sites. These in turn recruit Fanconi anemia (FA) proteins, including FANCM and BLM, to resolve the R-loop structure. Our findings suggest that PCAF, histone acetylation, and FA proteins collaborate to resolve R-loops and ensure genome stability. This study therefore provides novel mechanistic insights into the dynamics of R-loops as well as the role of PCAF in preserving genome stability. These results may help develop therapeutic strategies to target diseases associated with genome instability.
Related Topics
Concepts
PCAF
Biology
Acetylation
Histone
Genome instability
Genetics
Genome
CTCF
Cell biology
Computational biology
Transcription factor
DNA
DNA damage
Gene
Enhancer
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/nar/gkae558
- https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkae558/58343670/gkae558.pdf
- OA Status
- gold
- Cited By
- 15
- References
- 92
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4400140608
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4400140608Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1093/nar/gkae558Digital Object Identifier
- Title
-
PCAF promotes R-loop resolution via histone acetylationWork title
- Type
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-06-28Full publication date if available
- Authors
-
Seo Yun Lee, Soo Hyun Lee, Nak Hun Choi, Ja Young Kim, Jun Hee Kweon, Kyle M. Miller, Jae Jin KimList of authors in order
- Landing page
-
https://doi.org/10.1093/nar/gkae558Publisher landing page
- PDF URL
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https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkae558/58343670/gkae558.pdfDirect link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkae558/58343670/gkae558.pdfDirect OA link when available
- Concepts
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PCAF, Biology, Acetylation, Histone, Genome instability, Genetics, Genome, CTCF, Cell biology, Computational biology, Transcription factor, DNA, DNA damage, Gene, EnhancerTop concepts (fields/topics) attached by OpenAlex
- Cited by
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15Total citation count in OpenAlex
- Citations by year (recent)
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2025: 14, 2024: 1Per-year citation counts (last 5 years)
- References (count)
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92Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.thereby | 78 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.cellular | 7, 24 |
| abstract_inverted_index.diseases | 176 |
| abstract_inverted_index.dynamics | 153 |
| abstract_inverted_index.explores | 50 |
| abstract_inverted_index.findings | 127 |
| abstract_inverted_index.insights | 150 |
| abstract_inverted_index.multiple | 44 |
| abstract_inverted_index.promotes | 68 |
| abstract_inverted_index.proteins | 135 |
| abstract_inverted_index.provides | 147 |
| abstract_inverted_index.depletion | 67 |
| abstract_inverted_index.diseases, | 45 |
| abstract_inverted_index.essential | 17 |
| abstract_inverted_index.formation | 29 |
| abstract_inverted_index.important | 35 |
| abstract_inverted_index.including | 46, 117 |
| abstract_inverted_index.processes | 40 |
| abstract_inverted_index.proteins, | 116 |
| abstract_inverted_index.regulated | 33 |
| abstract_inverted_index.stability | 21 |
| abstract_inverted_index.therefore | 146 |
| abstract_inverted_index.associated | 177 |
| abstract_inverted_index.disrupting | 5 |
| abstract_inverted_index.especially | 74 |
| abstract_inverted_index.functions. | 8 |
| abstract_inverted_index.generation | 70 |
| abstract_inverted_index.preserving | 164 |
| abstract_inverted_index.processes. | 25 |
| abstract_inverted_index.regulating | 23 |
| abstract_inverted_index.resolution | 31 |
| abstract_inverted_index.stability, | 58 |
| abstract_inverted_index.stability. | 81, 143, 166 |
| abstract_inverted_index.strategies | 173 |
| abstract_inverted_index.structure. | 125 |
| abstract_inverted_index.collaborate | 136 |
| abstract_inverted_index.exonuclease | 103 |
| abstract_inverted_index.facilitates | 87 |
| abstract_inverted_index.maintaining | 19, 56 |
| abstract_inverted_index.mechanistic | 149 |
| abstract_inverted_index.recruitment | 93 |
| abstract_inverted_index.resolution. | 62 |
| abstract_inverted_index.structures, | 73 |
| abstract_inverted_index.therapeutic | 172 |
| abstract_inverted_index.acetylation, | 10, 90, 132 |
| abstract_inverted_index.compromising | 79 |
| abstract_inverted_index.instability, | 4 |
| abstract_inverted_index.instability. | 180 |
| abstract_inverted_index.particularly | 11 |
| abstract_inverted_index.specifically | 59 |
| abstract_inverted_index.Understanding | 26 |
| abstract_inverted_index.double-strand | 97 |
| abstract_inverted_index.dysregulation | 37 |
| abstract_inverted_index.transcription, | 77 |
| abstract_inverted_index.Mechanistically, | 82 |
| abstract_inverted_index.p300/CBP-associated | 13 |
| cited_by_percentile_year.max | 100 |
| cited_by_percentile_year.min | 90 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 7 |
| citation_normalized_percentile.value | 0.95756621 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |