Abstract
Regulation of the repair of DNA double-strand breaks by homologous recombination is extremely important for both cell viability and the maintenance of genomic integrity. Modulation of double-strand break repair in the yeast Saccharomyces cerevisiae involves controlling the recruitment of one of the central recombination proteins, Rad52, to sites of DNA lesions. The Rad52 protein, which plays a role in strand exchange and the annealing of single strand DNA, is positively regulated upon entry into S phase, repressed during the intra-S phase checkpoint, and undergoes posttranslational modification events such as phosphorylation and sumoylation. These processes all contribute to the timing of Rad52 recruitment, its stability and function. Here, we summarize the regulatory events affecting the Rad52 protein and discuss how this regulation impacts DNA repair and cell survival.
Highlights
Regulation of the repair of DNA double-strand breaks by homologous recombination is extremely important for both cell viability and the maintenance of genomic integrity
In synthesis-dependent strand annealing (SDSA, Figure 2B) new DNA synthesis occurs along only one strand, which is subsequently displaced by a DNA helicase
Even during HU arrest, IR-induced DNA breaks undergo enough resection to form RPA foci and still do not form Rad52 foci [47]. These results suggest that a simple model hinging on available RPA-bound single strand DNA (ssDNA) does not fully explain the complete absence of Rad52 foci we propose that the intra-S phase checkpoint imposes an additional level of regulation, suppressing Rad52 foci both at stalled replication forks and at Double-strand breaks (DSBs)
Summary
Regulation of Rad affects double strand break repair by initiating and/or directing many aspects of HR. These regulatory mechanisms help suppress potentially mutagenic or lethal recombination events in different ways. Entry into S phase may present a point in the cell cycle where the repair of a potentially lethal lesion such as a DSB that occurred in G1 must undergo non-conservative recombination before replication can proceed. At this stage, the cell may repair the DSB using the homologous chromosome as a template, again with the potential for loss of heterozygosity. The co-ordination of recombination in budding yeast revolves around the Rad protein for integration of checkpoint and cell cycle signals necessary to coordinate an appropriate repair response
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