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FANCM regulates DNA chain elongation and is stabilized by S‐phase checkpoint signalling
Author(s) -
LukeGlaser Sarah,
Luke Brian,
Grossi Simona,
Constantinou Angelos
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.371
Subject(s) - biology , g2 m dna damage checkpoint , elongation , dna , microbiology and biotechnology , signalling , genetics , cell cycle checkpoint , cell cycle , gene , materials science , ultimate tensile strength , metallurgy
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.