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Nucleic Acids Res. 2014 Feb;42(4):2380-90. doi: 10.1093/nar/gkt1263. Epub 2013 Dec 6.

Human RECQ5 helicase promotes repair of DNA double-strand breaks by synthesis-dependent strand annealing.

Author information

1
Institute of Molecular Cancer Research, University of Zurich, CH-8057 Zurich, Switzerland and Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 14300 Prague, Czech Republic.

Abstract

Most mitotic homologous recombination (HR) events proceed via a synthesis-dependent strand annealing mechanism to avoid crossing over, which may give rise to chromosomal rearrangements and loss of heterozygosity. The molecular mechanisms controlling HR sub-pathway choice are poorly understood. Here, we show that human RECQ5, a DNA helicase that can disrupt RAD51 nucleoprotein filaments, promotes formation of non-crossover products during DNA double-strand break-induced HR and counteracts the inhibitory effect of RAD51 on RAD52-mediated DNA annealing in vitro and in vivo. Moreover, we demonstrate that RECQ5 deficiency is associated with an increased occupancy of RAD51 at a double-strand break site, and it also causes an elevation of sister chromatid exchanges on inactivation of the Holliday junction dissolution pathway or on induction of a high load of DNA damage in the cell. Collectively, our findings suggest that RECQ5 acts during the post-synaptic phase of synthesis-dependent strand annealing to prevent formation of aberrant RAD51 filaments on the extended invading strand, thus limiting its channeling into potentially hazardous crossover pathway of HR.

PMID:
24319145
PMCID:
PMC3936725
DOI:
10.1093/nar/gkt1263
[Indexed for MEDLINE]
Free PMC Article

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