期刊
MOLECULAR CELL
卷 68, 期 2, 页码 414-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2017.09.036
关键词
-
资金
- Ines Mandl research fellowship
- NIH [4T32CA009503-30, F31CA210607, R01CA197774]
- Breast Cancer Alliance young investigator grant
- Ovarian Cancer Research Fund Alliance Liz Tilberis award [368964]
- Susan G. Komen career catalyst research grant [CCR16377030]
- AIRC-Associazione Italiana per Ricerca sul Cancro
- European Research Council [614541, 681630]
- Armenise-Harvard CDA
- Swiss National Science foundation [PP00P3_159323]
- American-Italian Cancer Foundation post-doctoral research fellowship
- Fondazione Veronesi
- European Research Council (ERC) [614541] Funding Source: European Research Council (ERC)
- Swiss National Science Foundation (SNF) [PP00P3_159323] Funding Source: Swiss National Science Foundation (SNF)
To ensure the completion of DNA replication and maintenance of genome integrity, DNA repair factors protect stalled replication forks upon replication stress. Previous studies have identified a critical role for the tumor suppressors BRCA1 and BRCA2 in preventing the degradation of nascent DNA by the MRE11 nuclease after replication stress. Here we show that depletion of SMARCAL1, a SNF2-family DNA translocase that remodels stalled forks, restores replication fork stability and reduces the formation of replication stress-induced DNA breaks and chromosomal aberrations in BRCA1/2-deficient cells. In addition to SMARCAL1, other SNF2-family fork remodelers, including ZRANB3 and HLTF, cause nascent DNA degradation and genomic instability in BRCA1/2-deficient cells upon replication stress. Our observations indicate that nascent DNA degradation in BRCA1/2-deficient cells occurs as a consequence of MRE11-dependent nucleolytic processing of reversed forks generated by fork remodelers. These studies provide mechanistic insights into the processes that cause genome instability in BRCA1/2-deficient cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据