Ryan B. Jensen
Yale University
Homologous recombinationGeneNucleotide excision repairReplication protein ADNA repairDNA damageDNA repair protein XRCC4Molecular biologyGenome instabilityChemistryRAD51BRCA2 ProteinRecombinant DNAMutationGeneticsDNADNA mismatch repairHomologous chromosomeMedicineBiologyCell biology
23Publications
12H-index
1,343Citations
Publications 26
Newest
#1Judit Jimenez-Sainz (Yale University)H-Index: 4
#2Joshua Mathew (Yale University)
Last. Ryan B. Jensen (Yale University)H-Index: 12
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BRCA2 is a tumor suppressor gene that maintains genome stability by mediating the high fidelity repair of DNA double-strand breaks (DSBs) through homology-directed repair (HDR). Pathogenic mutations in BRCA2 predispose to breast, ovarian, pancreatic, prostate, and other cancers. Mutations in BRCA2 leading to severe protein truncation predict pathogenicity, however, missense mutations with unknown functional consequences, designated Variants of Uncertain Significance (VUS), comprise 60% of BRCA2 ...
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#1Karl E Zahn (Yale University)
#2Ryan B. JensenH-Index: 12
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 step of a DNA double-strand break repair pathway able to join 5′-resected substrates by locating and pairing microhomologies present in 3′-overhanging single-stranded tails, cleaving the extraneous 3′-DNA by dNTP-dependent end-processing, before extending the ...
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Abstract null null Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) is mutated frequently in gliomas and represents a potential target for cancer therapies. ATRX is known to function as a histone chaperone that helps incorporate histone variant, H3.3, into the genome. Studies have implicated ATRX in key DNA damage response (DDR) pathways but a distinct role in DNA repair has yet to be fully elucidated. To further investigate the function of ATRX in the DDR, we created isogenic wild-...
1 CitationsSource
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. BRCA2 is an essential protein that mediates the loading of RAD51 onto resected DNA breaks, a key step in HDR. Germline mutations in BRCA2 are associated with an increased risk for breast, ovarian, prostate, and pancreatic cancer. Clinical findings of germline or s...
1 CitationsSource
#1Karl E. Zahn (UVM: University of Vermont)H-Index: 6
#2Ryan B. Jensen (Yale University)H-Index: 12
Last. Sylvie Doublié (UVM: University of Vermont)H-Index: 35
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Summary Cancers with hereditary defects in homologous recombination rely on DNA polymerase θ (pol θ) for repair of DNA double-strand breaks. During end joining, pol θ aligns microhomology tracts internal to 5′-resected broken ends. An unidentified nuclease trims the 3′ ends before synthesis can occur. Here we report that a nuclease activity, which differs from the proofreading activity often associated with DNA polymerases, is intrinsic to the polymerase domain of pol θ. Like the DNA synthesis a...
10 CitationsSource
#1Sudipta Lahiri (Yale University)H-Index: 1
#2Ryan B. Jensen (Yale University)H-Index: 12
The homologous recombination (HR) pathway maintains genomic integrity by repairing DNA double-strand breaks (DSBs), single-strand DNA gaps, and collapsed replication forks. The process of HR involves strand invasion, homology search, and DNA strand exchange between paired DNA molecules. HR is critical for the high-fidelity repair of DNA DSBs in mitotic cells and for the exchange of genetic information during meiosis. Here we describe a DNA strand exchange reaction in vitro utilizing purified pro...
2 CitationsSource
#1Jennifer GarbarinoH-Index: 1
#2Ranjit S. BindraH-Index: 30
Last. Ryan B. JensenH-Index: 12
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#1Ryan B. Jensen (Yale University)H-Index: 12
#2Eli Rothenberg (NYU: New York University)H-Index: 28
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, and other cellular activities contribute to the delicate spatiotemporal control that cells utilize to regulate and maintain genome stability. This perspective will highlight DNA double-strand break (DSB) repair pathways in human cells, how DNA repair failures c...
8 CitationsSource
#1Charles Wang (University of Texas MD Anderson Cancer Center)
#2Judit Jimenez-Sainz (Yale University)H-Index: 4
Last. Alexander A. Mazin (Drexel University)
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Homologous Recombination (HR) is a high-fidelity process with a range of biologic functions from generation of genetic diversity to repair of DNA double-strand breaks (DSBs). In mammalian cells, BRCA2 facilitates the polymerization of RAD51 onto ssDNA to form a presynaptic nucleoprotein filament. This filament can then strand invade a homologous dsDNA to form the displacement loop (D-loop) structure leading to the eventual DSB repair. This pro-recombinatory feature of RAD51-BRCA2 is well documen...
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#1Charles X. Wang (Drexel University)H-Index: 2
#2Judit Jimenez-Sainz (Yale University)H-Index: 4
Last. Alexander V. Mazin (Drexel University)H-Index: 39
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Homologous Recombination (HR) is a high-fidelity process with a range of biologic functions from generation of genetic diversity to repair of DNA double-strand breaks (DSBs). In mammalian cells, BRCA2 facilitates the polymerization of RAD51 onto ssDNA to form a presynaptic nucleoprotein filament. This filament can then strand invade a homologous dsDNA to form the displacement loop (D-loop) structure leading to the eventual DSB repair. Here, we have found that RAD51 in stoichiometric excess over ...
1 CitationsSource