FANCM regulates DNA chain elongation and is stabilized by S-phase checkpoint signalling.

Details

Serval ID
serval:BIB_5F815B15C01D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
FANCM regulates DNA chain elongation and is stabilized by S-phase checkpoint signalling.
Journal
EMBO Journal
Author(s)
Luke-Glaser S., Luke B., Grossi S., Constantinou A.
ISSN
1460-2075[electronic], 0261-4189[linking]
Publication state
Published
Issued date
2010
Volume
29
Number
4
Pages
795-805
Language
english
Abstract
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.
Keywords
Adenosine Triphosphatases/metabolism, Base Sequence, DNA/biosynthesis, DNA/genetics, DNA Damage, DNA Helicases/antagonists & inhibitors, DNA Helicases/genetics, DNA Repair, DNA Replication/physiology, Fanconi Anemia Complementation Group D2 Protein/antagonists & inhibitors, Fanconi Anemia Complementation Group D2 Protein/genetics, Hela Cells, Humans, Models, Biological, Proteasome Endopeptidase Complex/metabolism, Protein Kinases/metabolism, RNA, Small Interfering/genetics, S Phase, Signal Transduction
Pubmed
Web of science
Open Access
Yes
Create date
14/09/2010 14:11
Last modification date
20/08/2019 14:17
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