Ryan B. Jensen
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View article: RAD51 Paralogs and RAD51 Paralog Complexes BCDX2 and CX3 Interact with BRCA2
RAD51 Paralogs and RAD51 Paralog Complexes BCDX2 and CX3 Interact with BRCA2 Open
Homologous recombination (HR) is an important mechanism for repairing DNA double-strand breaks (DSBs) and preserving genome integrity. Pathogenic mutations in the HR proteins BRCA2 and the RAD51 paralogs predispose individuals to breast, o…
View article: Cell cycle regulation of polymerase theta mediated end-joining underlies its sensitivity to loss of BLM-DNA2
Cell cycle regulation of polymerase theta mediated end-joining underlies its sensitivity to loss of BLM-DNA2 Open
DNA double-strand breaks (DSBs) are predominantly resolved by the error-prone non-homologous end-joining (NHEJ) or high-fidelity homologous recombination (HR) DNA repair pathways. NHEJ involves minimal end-processing and drives direct liga…
View article: PARG inhibition induces nuclear aggregation of PARylated PARP1
PARG inhibition induces nuclear aggregation of PARylated PARP1 Open
PARG inhibitors are currently under clinical development for the treatment of DNA repair-deficient cancers, however, their precise mechanism of action is still unclear. Here we report that PARG inhibition causes increased nuclear PARylated…
View article: BRCA2 chaperones RAD51 to single molecules of RPA-coated ssDNA
BRCA2 chaperones RAD51 to single molecules of RPA-coated ssDNA Open
Mutations in the breast cancer susceptibility gene, BRCA2 , greatly increase an individual’s lifetime risk of developing breast and ovarian cancers. BRCA2 suppresses tumor formation by potentiating DNA repair via homologous recombination. …
View article: BRCA2 chaperones RAD51 to single molecules of RPA-coated ssDNA
BRCA2 chaperones RAD51 to single molecules of RPA-coated ssDNA Open
Mutations in the breast cancer susceptibility gene, BRCA2, greatly increase an individual’s lifetime risk of developing breast and ovarian cancers. BRCA2 suppresses tumor formation by potentiating DNA repair via homologous recombination. C…
View article: BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair
BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair Open
Pathogenic mutations in the BRCA2 tumor suppressor gene predispose to breast, ovarian, pancreatic, prostate, and other cancers. BRCA2 maintains genome stability through homology-directed repair (HDR) of DNA double-strand breaks (DSBs) and …
View article: The Pathogenic R3052W BRCA2 Variant Disrupts Homology-Directed Repair by Failing to Localize to the Nucleus
The Pathogenic R3052W BRCA2 Variant Disrupts Homology-Directed Repair by Failing to Localize to the Nucleus Open
The BRCA2 germline missense variant, R3052W, resides in the DNA binding domain and has been previously classified as a pathogenic allele. In this study, we sought to determine how R3052W alters the cellular functions of BRCA2 in the DNA da…
View article: DNA fiber combing protocol using in-house reagents and coverslips to analyze replication fork dynamics in mammalian cells
DNA fiber combing protocol using in-house reagents and coverslips to analyze replication fork dynamics in mammalian cells Open
DNA fiber combing is a versatile technique that provides insight into replication fork dynamics at single-molecule resolution. DNA fibers are bound to silanized coverslips and combed, which straightens and aligns the fibers along a single …
View article: BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair
BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair Open
Pathogenic mutations in the BRCA2 tumor suppressor gene predispose to breast, ovarian, pancreatic, prostate, and other cancers. BRCA2 maintains genome stability through homology-directed repair (HDR) of DNA double-strand breaks (DSBs) and …
View article: Polymerase θ Coordinates Multiple Intrinsic Enzymatic Activities during DNA Repair
Polymerase θ Coordinates Multiple Intrinsic Enzymatic Activities during DNA Repair Open
The POLQ gene encodes DNA polymerase θ, a 2590 amino acid protein product harboring DNA-dependent ATPase, template-dependent DNA polymerase, dNTP-dependent endonuclease, and 5′–dRP lyase functions. Polymerase θ participates at an essential…
View article: Imprecise Medicine: BRCA2 Variants of Uncertain Significance (VUS), the Challenges and Benefits to Integrate a Functional Assay Workflow with Clinical Decision Rules
Imprecise Medicine: BRCA2 Variants of Uncertain Significance (VUS), the Challenges and Benefits to Integrate a Functional Assay Workflow with Clinical Decision Rules Open
Pathological mutations in homology-directed repair (HDR) genes impact both future cancer risk and therapeutic options for patients. HDR is a high-fidelity DNA repair pathway for resolving DNA double-strand breaks throughout the genome. BRC…
View article: Preserving genome integrity in human cells via DNA double-strand break repair
Preserving genome integrity in human cells via DNA double-strand break repair Open
The efficient maintenance of genome integrity in the face of cellular stress is vital to protect against human diseases such as cancer. DNA replication, chromatin dynamics, cellular signaling, nuclear architecture, cell cycle checkpoints, …
View article: A cell-penetrating antibody inhibits human RAD51 via direct binding
A cell-penetrating antibody inhibits human RAD51 via direct binding Open
RAD51, a key factor in homology-directed repair (HDR), has long been considered an attractive target for cancer therapy, but few specific inhibitors have been found. A cell-penetrating, anti-DNA, lupus autoantibody, 3E10, was previously sh…
View article: The Tumor-Associated Variant RAD51 G151D Induces a Hyper-Recombination Phenotype
The Tumor-Associated Variant RAD51 G151D Induces a Hyper-Recombination Phenotype Open
The RAD51 protein plays a key role in the homology-directed repair of DNA double-strand breaks and is important for maintaining genome stability. Here we report on a novel human RAD51 variant found in an aggressive and therapy-refractive b…
View article: Distinct binding of BRCA2 BRC repeats to RAD51 generates differential DNA damage sensitivity
Distinct binding of BRCA2 BRC repeats to RAD51 generates differential DNA damage sensitivity Open
BRCA2 is a multi-faceted protein critical for the proper regulation of homology-directed repair of DNA double-strand breaks. Elucidating the mechanistic features of BRCA2 is crucial for understanding homologous recombination and how patien…