세미나/행사

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세미나 담당교수 : 2023-2학기 김진홍 (금요세미나, 콜로퀴움, jinhkim@snu.ac.kr), 강찬희 (신진과학자세미나, chanhee.kang@snu.ac.kr), 윤태영 (10-10 project, tyyoon@snu.ac.kr)
조 교 : 장사라 (02-880-4431, jsarah@snu.ac.kr)
호암교수회관 : 5572, 교수회관: 5241, 두레미담: 9358, 라쿠치나: 1631.

[초청강연] Redefining therapy response in BRCA cancer

2019-11-05l 조회수 2964

일시: 2019-11-15 16:00 ~ 17:00
발표자: Prof. Sharon Cantor (University of Massachusetts Medical School)
담당교수: Prof. Hyunsook Lee
장소: Bldg 500, Mok-Am Hall
Abstract:
BRCA1 or BRCA2 (BRCA)-deficient tumor cells have defects in DNA repair by homologous recombination and DNA replication fork stability that is thought to underlie poly(ADP) ribose polymerase, PARP inhibitor (PARPi) sensitivity. However, new findings indicate that PARPi do not initially generate DNA breaks or pause replication forks, but rather accelerate DNA replication forks. Thus, we tested the hypothesis that sensitivity results from combined replication dysfunction. Consistent with this interpretation, here we demonstrate that PARPi-induced replication acceleration is exacerbated in BRCA deficient cells, but avoided in cells that are not sensitive to PARPi. Furthermore, in BRCA deficient -tissue culture and -patient tumors and in known and de novo models of PARPi resistance, we find that this replication dysfunction is suppressed. Collectively a molecular link between PARPi sensitivity and replication dysfunction provides a new paradigm for understanding synthetic lethal interactions in BRCA cancer.