The Fanconi anemia protein FANCM can promote branch migration of Holliday junctions and replication forks

Kerstin Gari; Chantal Décaillet; Alicja Z Stasiak; Andrzej Stasiak; Angelos Constantinou

doi:10.1016/j.molcel.2007.11.032

The Fanconi anemia protein FANCM can promote branch migration of Holliday junctions and replication forks

Mol Cell. 2008 Jan 18;29(1):141-8. doi: 10.1016/j.molcel.2007.11.032.

Authors

Kerstin Gari¹, Chantal Décaillet, Alicja Z Stasiak, Andrzej Stasiak, Angelos Constantinou

Affiliation

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

PMID: 18206976
DOI: 10.1016/j.molcel.2007.11.032

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate / metabolism
Adenylyl Imidodiphosphate / metabolism
Animals
Cell Line / chemistry
Chromatography, Affinity
DNA Helicases / genetics
DNA Helicases / isolation & purification
DNA Helicases / physiology*
DNA Helicases / ultrastructure
DNA Replication / physiology*
DNA, Cruciform / metabolism*
DNA-Binding Proteins / physiology
Dimerization
Electrophoretic Mobility Shift Assay
Fanconi Anemia Complementation Group Proteins
Humans
Microscopy, Electron
Oligodeoxyribonucleotides / chemical synthesis
Oligodeoxyribonucleotides / metabolism
Protein Binding
Recombinant Fusion Proteins / isolation & purification
Recombinant Fusion Proteins / physiology
Recombination, Genetic / physiology*
Spodoptera
Substrate Specificity

Substances

DNA, Cruciform
DNA-Binding Proteins
FAAP24 protein, human
Fanconi Anemia Complementation Group Proteins
Oligodeoxyribonucleotides
Recombinant Fusion Proteins
Adenylyl Imidodiphosphate
Adenosine Triphosphate
FANCM protein, human
DNA Helicases