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

0436398 - ÚMG 2015 RIV GB eng J - Journal Article
Paliwal, S. - Kanagaraj, R. - Sturzenegger, A. - Burdová, Kamila - Janščák, Pavel
Human RECQ5 helicase promotes repair of DNA double-strand breaks by synthesis-dependent strand annealing.
Nucleic Acids Research. Roč. 42, č. 4 (2014), s. 2380-2390. ISSN 0305-1048. E-ISSN 1362-4962
R&D Projects: GA ČR GA204/09/0565; GA ČR GAP305/10/0281
Grant - others:Swiss National Science Foundation(CH) 31003A-129747; Swiss National Science Foundation(CH) 31003A_146206
Institutional support: RVO:68378050
Keywords : Human RECQ5 helicase * DNA double-strand breaks * mitotic homologous recombination
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 9.112, year: 2014

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.
Permanent Link: http://hdl.handle.net/11104/0241967