Hong Yan, PhD
Office Phone: 215-728-2514
Lab Phone: 215-728-2575
DNA double-strand breaks (DSBs) are among the most deleterious damages to the genome. If unrepaired or improperly repaired, DSBs might lead to gross genomic instability and ultimately many human diseases such as immunodeficiency, premature aging, and, most importantly, cancer. Somewhat paradoxically, cancer cells are also hypersensitive to many chemotherapeutic drugs that act by inducing DSBs. The main focus of our research is to understand the mechanism of DSB repair.
There are four major pathways to repair DSBs in eukaryotes: non-homologous end joining (NHEJ), homologous recombination (HR), single-strand annealing (SSA), and alternative end joining (alt-EJ). The key step in the choice of different DSB repair pathways is the initial processing of DNA ends. NHEJ involves limited processing, but the other three pathways require the resection of 5’ strands to generate 3’ ss-DNA tails. We have found that a major mechanism for resection is carried out by the combined actions of a RecQ-type DNA helicase, the DNA2 ss-DNA nuclease, and the eukaryotic ss-DNA binding protein RPA. The helicase first unwinds the end and DNA2 then degrades the 5’ ss-tail. Both enzymes are stimulated by RPA via physical interactions. Our current research aims to understand how the structure of DNA ends affects the choice of DSB repair pathways and the mechanism of resection and resection-mediated repair.