DNA DAMAGE CHECKPOINT MEDIATED REGULATION OF DOUBLE-STRAND BREAK REPAIR

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 DNA损伤检查点协调细胞对遗传毒性应激的反应，并响应于DNA损伤和复制叉停滞而阻止细胞周期。同源重组是DNA双链断裂和其他检查点诱导损伤修复的普遍途径。此外，同源重组参与DNA损伤的复制后耐受和复制叉停滞后DNA复制的恢复。在这里，我们表明，Rad 55蛋白的丝氨酸2，8和14（S2，8，14）上的磷酸化是生存以及在全基因组遗传毒性应激下的正常生长所必需的。Rad 55是酿酒酵母中的Rad 51蛋白，在Rad 51丝的组装中起作用，Rad 51丝是重组DNA修复的中心中间体。磷酸化缺陷的rad 55-S2，8，14 A突变体在DNA损伤条件下显示出非常缓慢的S期穿越，这可能是由于停滞的复制叉的恢复较慢或复制相关DNA损伤的修复较慢。这些结果表明，Rad 55-S2，8，14磷酸化激活重组修复，允许基因毒性应激后更快的恢复。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DNA damage checkpoints coordinate the cellular response to genotoxic stress and arrest the cell cycle in response to DNA damage and replication fork stalling. Homologous recombination is a ubiquitous pathway for the repair of DNA double-stranded breaks and other checkpoint-inducing lesions. Moreover, homologous recombination is involved in postreplicative tolerance of DNA damage and the recovery of DNA replication after replication fork stalling. Here, we show that the phosphorylation on serines 2, 8, and 14 (S2,8,14) of the Rad55 protein is specifically required for survival as well as for normal growth under genome-wide genotoxic stress. Rad55 is a Rad51 paralog in Saccharomyces cerevisiae and functions in the assembly of the Rad51 filament, a central intermediate in recombinational DNA repair. Phosphorylation-defective rad55-S2,8,14A mutants display a very slow traversal of S phase under DNA-damaging conditions, which is likely due to the slower recovery of stalled replication forks or the slower repair of replication-associated DNA damage. These results suggest that Rad55-S2,8,14 phosphorylation activates recombinational repair, allowing for faster recovery after genotoxic stress.