Informace o publikaci
Unloading of homologous recombination factors is required for restoring double-stranded DNA at damage repair loci
| Autoři | |
|---|---|
| Rok publikování | 2017 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | EMBO Journal |
| Fakulta / Pracoviště MU | |
| Citace | |
| Doi | http://dx.doi.org/10.15252/embj.201694628 |
| Obor | Genetika a molekulární biologie |
| Klíčová slova | DNA resynthesis; PCNA; Rad51; recombination machinery; Srs2 |
| Popis | Cells use homology-dependent DNA repair to mend chromosome breaks and restore broken replication forks, thereby ensuring genome stability and cell survival. DNA break repair via homologybased mechanisms involves nuclease-dependent DNA end resection, which generates long tracts of single-stranded DNA required for checkpoint activation and loading of homologous recombination proteins Rad52/51/55/57. While recruitment of the homologous recombination machinery is well characterized, it is not known how its presence at repair loci is coordinated with downstream resynthesis of resected DNA. We show that Rad51 inhibits recruitment of proliferating cell nuclear antigen (PCNA), the platform for assembly of the DNA replication machinery, and that unloading of Rad51 by Srs2 helicase is required for efficient PCNA loading and restoration of resected DNA. As a result, srs2D mutants are deficient in DNA repair correlating with extensive DNA processing, but this defect in srs2D mutants can be suppressed by inactivation of the resection nuclease Exo1. We propose a model in which during re-synthesis of resected DNA, the replication machinery must catch up with the preceding processing nucleases, in order to close the single-stranded gap and terminate further resection. |
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