Vol 42: Human RECQ5 helicase promotes repair of DNA double-strand breaks by synthesis-dependent strand annealing.Reportar como inadecuado



 Vol 42: Human RECQ5 helicase promotes repair of DNA double-strand breaks by synthesis-dependent strand annealing.


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This article is from Nucleic Acids Research, volume 42.AbstractMost 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.



Autor: Paliwal, Shreya; Kanagaraj, Radhakrishnan; Sturzenegger, Andreas; Burdova, Kamila; Janscak, Pavel

Fuente: https://archive.org/







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