期刊
EMBO JOURNAL
卷 29, 期 4, 页码 795-805出版社
WILEY
DOI: 10.1038/emboj.2009.371
关键词
DNA replication; FANCM; Fanconi anemia; fork regression
资金
- Marie Heim-Vogtlin fellowship of the Swiss National Science Foundation (SNSF) [PMPDA3118607]
- SNSF professorship [PP00A-118991]
FANCM binds and remodels replication fork structures in vitro. We report that in vivo, FANCM controls DNA chain elongation in an ATPase-dependent manner. In the presence of replication inhibitors that do not damage DNA, FANCM counteracts fork movement, possibly by remodelling fork structures. Conversely, through damaged DNA, FANCM promotes replication and recovers stalled forks. Hence, the impact of FANCM on fork progression depends on the underlying hindrance. We further report that signalling through the checkpoint effector kinase Chk1 prevents FANCM from degradation by the proteasome after exposure to DNA damage. FANCM also acts in a feedback loop to stabilize Chk1. We propose that FANCM is a ringmaster in the response to replication stress by physically altering replication fork structures and by providing a tight link to S-phase checkpoint signalling. The EMBO Journal (2010) 29, 795-805. doi: 10.1038/emboj.2009.371; Published online 10 December 2009
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