Speaker: Patrick Sung, Ph.D., Professor, Biochemistry & Structural Biology, Director, Greehey Children's Cancer Research Institute

Time: 13:00-14:30 p.m., Oct 28, 2024, GMT+8

Venue: Youcai Deng Lecture Hall, School of Life Sciences, PKU

Abstract: 

The licensing step of DNA double-strand break (DSB) repair by homologous recombination entails resection of DNA ends to generate a ssDNA template for assembling the repair machinery consisting of the RAD51 recombinase. DNA end resection is mechanistically intricate and reliant on the tumor suppressor complex BRCA1-BARD1. Specifically, three distinct nuclease entities, viz, the 5'-3' exonuclease EXO1 and heterodimeric complexes of the DNA endonuclease DNA2 with either the BLM or WRN helicase, act in synergy to execute the end resection process. With purified protein factors, we show that BRCA1-BARD1 physically interacts with EXO1, BLM, and WRN and that it upregulates the activity of all three resection pathways. We also demonstrate that BRCA1 and BARD1 harbor standalone modules that contribute to the overall functionality of BRCA1-BARD1. Moreover, analysis of a BARD1 mutant impaired in DNA binding reveals the importance of this BARD1 attribute in end resection in vitro and in cells. Thus, BRCA1-BARD1 licenses the engagement of homologous recombination in DSB repair by upregulating long-range DNA end resection.

Source: School of Life Sciences