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Physical interactions of Rad51 and Rad52 with Mcm2-7 coordinate their binding to chromatin during the cell cycle and In response to DNA damage

AutorCano-Linares, María I.; Cabello-Lobato, María J. ; González-Prieto, Román ; Prado, Félix
Palabras claveChromatin
Homologous recombination
Replication
Fecha de publicación2017
Citación28th International Conference on Yeast Genetics and Molecular Biology (2017)
ResumenThe recombination proteins Rad51 and Rad52 help the fork to bypass blocking lesions and fill in the gaps of single-stranded DNA (ssDNA) generated during this process of DNA damage tolerance (DDT). In contrast to DNA double-strand breaks, Rad51 and Rad52 recruitment to the ssDNA lesions must occur during S phase. Here we show that Rad51 and Rad52 physically interact with the replicative helicase Mcm2-7 in G1. These interactions are lost during replication unless cells divide in the presence of replicative blocking lesions. They occur mostly in chromatin but are prevented at the pre-RC and at the replication forks, suggesting that Rad51 and Rad52 interact with the excess of Mcm2-7 helicases loaded in G1 and spread to the vicinity of the replication origins. Indeed, Mcm2-7 and Rad51 accumulate at a nuclease-insoluble chromatin fraction enriched in replication factors. Notably, these interactions coordinate the kinetics of chromatin binding of Mcm2-7, Rad51 and Rad52, which accumulate in G1, are released during S/G2 and are maintained in the presence of replicative DNA damage. This chromatin binding behavior is remarkable because homologous recombination is inactive in G1 and active during S/G2. Interestingly, the kinase activity of Cdc7 is required to preserve both the integrity of the Mcm2-7/Rad51/Rad52 complexes and the presence of these factors at chromatin during S/G2. Our results suggest novel roles for Cdc7 and Mcm2-7 in the regulation of the location of recombination proteins during DDT.
DescripciónResumen del póster presentado a la 28th International Conference on Yeast Genetics and Molecular Biology (ICYGMB), celebrada en Praga (Czech Republic) del 27 de agosto al 1 de septiembre de 2017.
URIhttp://hdl.handle.net/10261/165970
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