北京大学定量生物学中心

学术报告

题 目: Multi-faceted Role of BRCA1-BARD1 in DSB Repair Licensing

报告人: Patrick Sung, Ph.D.

Professor, Biochemistry & Structural Biology

Director, Greehey Children's Cancer Research Institute

University of Texas Health Science Center at San Antonio

时 间: 10月28日（周一）13:00-14:00

地 点: 金光生命科学大楼邓祐才报告厅

主持人: 齐志研究员 & 李晴教授

摘要:

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.

报告人简介：

As a doctoral student at Oxford University, Professor Sung, Patrick received training in protein biochemistry and enzymology. When he was a postdoctoral fellow at the University of Rochester, he was able to reconstitute nucleotide excision repair in vitro. Since establishing his own laboratory in 1993, he has strived to understand how cells engage homologous recombination (HR) as tool in eliminating DNA breaks and crosslinks. The efficiency of HR catalyzed by the RAD51 recombinase is regulated by the tumor suppressors BRCA1, BARD1, and BRCA2, providing compelling evidence for a key role of HR in cancer avoidance. His studies have led to many original findings. To date, Patrick has published 314 articles, with 262 of them being original research papers. According to Scopus, his h-index is 87 with >26,060 citations, while Google Scholar reports an h-index of 105 with >38,590 citations. Patrick has accrued extensive leadership experience, having served as journal editor or associate editor (Molecular & Cellular Biology and the Journal of Biological Chemistry), NCI Training Grant Co-director, NIH study section chair (Cancer Etiology), Department Chair (Yale University and University of Texas), and as the current Director of the Greehey Children’s Cancer Research Institute. He has played a leading role in teaching, advising, and mentoring undergraduate and graduate students, postdoctoral fellows, and junior faculty at Yale University and the University of Texas. He is the recipient of prestigious mentorship awards at his current institution. To date, he has successfully mentored 25 postdoctoral fellows and 14 PhD students, all of whom have remained in academic science or are gainfully employed in industry. A significant number of his former trainees are now productive faculty at excellent institutions in the United States or abroad. Patrick is the Director of a newly funded Program Project Grant from the National Cancer Institute.