title: Human RECQ5 helicase promotes repair of DNA double-strand breaks by synthesis-dependent strand annealing.
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.
authors: 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.
authors: Shreya
authors: S
authors: Paliwal
authors: Radhakrishnan
authors: R
authors: Kanagaraj
authors: Andreas
authors: A
authors: Sturzenegger
authors: Kamila
authors: K
authors: Burdova
authors: Pavel
authors: P
authors: Janscak
mesh_terms: D002460:Cell Line; D004247:DNA / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004277:DNA, Single-Stranded / Q000378:metabolism; D006801:Humans; D051135:Rad51 Recombinase / Q000378:metabolism; D051721:Rad52 DNA Repair and Recombination Protein / Q000378:metabolism; D053484:RecQ Helicases / Q000378:metabolism*; D059767:Recombinational DNA Repair; D012854:Sister Chromatid Exchange
chemical_list: D004277:DNA, Single-Stranded; C506732:RECQL5 protein, human; D051721:Rad52 DNA Repair and Recombination Protein; D004247:DNA; D051135:Rad51 Recombinase; D053484:RecQ Helicases