A5103633025- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
University of Pittsburgh
2022
UPMC Hillman Cancer Center
2016-2021
Homology-directed repair (HDR), a critical DNA pathway in mammalian cells, is complex, leading to multiple outcomes with different impacts on genomic integrity. However, the factors that control these are often not well understood. Here we show SWS1-SWSAP1-SPIDR controls distinct types of HDR. Despite their requirement for stable assembly RAD51 recombinase at damage sites, proteins essential intra-chromosomal HDR, providing insight into why patients and mice mutations viable. inter-homolog...
Mutations in homologous recombination (HR) genes, including BRCA1 , BRCA2 and the RAD51 paralog RAD51C predispose to tumorigenesis sensitize cancers DNA-damaging agents poly(ADP ribose) polymerase inhibitors. However, ∼800 missense variants of unknown significance have been identified for alone, impairing cancer risk assessment therapeutic strategies. Here, we interrogated >50 variants, finding that mutations residues conserved with strongly predicted HR deficiency disrupted interactions...
Abstract Homology-directed repair (HDR), a critical DNA pathway in mammalian cells, is complex, leading to multiple outcomes with different impacts on genomic integrity. However, the factors that control these are often not well understood. Here we show SWS1-SWSAP1-SPIDR controls distinct types of HDR. Despite their requirement for stable assembly RAD51 recombinase at damage sites, proteins essential intra-chromosomal HDR, providing insight into why patients and mice mutations viable....