霍利迪路口
生物
范科尼贫血
分支迁移
DNA
DNA复制
细胞生物学
DNA修复
基因组不稳定性
遗传学
复制蛋白A
DNA结合蛋白
DNA损伤
基因
转录因子
作者
Kerstin Gari,Chantal Décaillet,Alicja Z. Stasiak,Andrzej Stasiak,Angelos Constantinou
出处
期刊:Molecular Cell
[Elsevier]
日期:2008-01-01
卷期号:29 (1): 141-148
被引量:231
标识
DOI:10.1016/j.molcel.2007.11.032
摘要
Fanconi anemia (FA) is a genetically heterogeneous cancer-prone disorder associated with chromosomal instability and cellular hypersensitivity to DNA crosslinking agents. The FA pathway is suspected to play a crucial role in the cellular response to DNA replication stress. At a molecular level, however, the function of most of the FA proteins is unknown. FANCM displays DNA-dependent ATPase activity and promotes the dissociation of DNA triplexes, but the physiological significance of this activity remains elusive. Here we show that purified FANCM binds to Holliday junctions and replication forks with high specificity and promotes migration of their junction point in an ATPase-dependent manner. Furthermore, we provide evidence that FANCM can dissociate large recombination intermediates, via branch migration of Holliday junctions through 2.6 kb of DNA. Our data suggest a direct role for FANCM in DNA processing, consistent with the current view that FA proteins coordinate DNA repair at stalled replication forks.
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