期刊
NUCLEIC ACIDS RESEARCH
卷 41, 期 13, 页码 6444-6459出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkt348
关键词
-
资金
- National Science Foundation [1121023]
- American Cancer Society [RSG-13-039-01-DMC]
- Leukemia Research Fund (Masonic Cancer Center)
- American Heart Association
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1121023] Funding Source: National Science Foundation
Fanconi Anemia (FA) and Bloom Syndrome share overlapping phenotypes including spontaneous chromosomal abnormalities and increased cancer predisposition. The FA protein pathway comprises an upstream core complex that mediates recruitment of two central players, FANCD2 and FANCI, to sites of stalled replication forks. Successful fork recovery depends on the Bloom's helicase BLM that participates in a larger protein complex ('BLMcx') containing topoisomerase III alpha, RMI1, RMI2 and replication protein A. We show that FANCD2 is an essential regulator of BLMcx functions: it maintains BLM protein stability and is crucial for complete BLMcx assembly; moreover, it recruits BLMcx to replicating chromatin during normal S-phase and mediates phosphorylation of BLMcx members in response to DNA damage. During replication stress, FANCD2 and BLM cooperate to promote restart of stalled replication forks while suppressing firing of new replication origins. In contrast, FANCI is dispensable for FANCD2-dependent BLMcx regulation, demonstrating functional separation of FANCD2 from FANCI.
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