期刊
SCIENCE
卷 326, 期 5960, 页码 1698-1701出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1182372
关键词
-
资金
- NIH [GM62267]
- Leukemia and Lymphoma Society [1406-07]
- New York State of Science, Technology and Academic Research (NYSTAR) [C040069]
- Swiss Cancer League [OCS-01413-08-2003]
- Dutch Cancer Society [T32CA09216]
- Burroughs Wellcome Fund
- Max Planck Institute
Fanconi anemia is a human cancer predisposition syndrome caused by mutations in 13 Fanc genes. The disorder is characterized by genomic instability and cellular hypersensitivity to chemicals that generate DNA interstrand cross-links (ICLs). A central event in the activation of the Fanconi anemia pathway is the mono-ubiquitylation of the FANCI-FANCD2 complex, but how this complex confers ICL resistance remains enigmatic. Using a cell-free system, we showed that FANCI-FANCD2 is required for replication-coupled ICL repair in S phase. Removal of FANCD2 from extracts inhibits both nucleolytic incisions near the ICL and translesion DNA synthesis past the lesion. Reversal of these defects requires ubiquitylated FANCI-FANCD2. Our results show that multiple steps of the essential S-phase ICL repair mechanism fail when the Fanconi anemia pathway is compromised.
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