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Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16107-12. doi: 10.1073/pnas.0804777105. Epub 2008 Oct 8.

Remodeling of DNA replication structures by the branch point translocase FANCM.

Author information

1
Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges s/Lausanne, Switzerland.

Abstract

Fanconi anemia (FA) is a genetically heterogeneous chromosome instability syndrome associated with congenital abnormalities, bone marrow failure, and cancer predisposition. Eight FA proteins form a nuclear core complex, which promotes tolerance of DNA lesions in S phase, but the underlying mechanisms are still elusive. We reported recently that the FA core complex protein FANCM can translocate Holliday junctions. Here we show that FANCM promotes reversal of model replication forks via concerted displacement and annealing of the nascent and parental DNA strands. Fork reversal by FANCM also occurs when the lagging strand template is partially single-stranded and bound by RPA. The combined fork reversal and branch migration activities of FANCM lead to extensive regression of model replication forks. These observations provide evidence that FANCM can remodel replication fork structures and suggest a mechanism by which FANCM could promote DNA damage tolerance in S phase.

PMID:
18843105
PMCID:
PMC2570989
DOI:
10.1073/pnas.0804777105
[Indexed for MEDLINE]
Free PMC Article

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