Bellaoui Mohammed, Chang Michael, Ou Jiongwen, Xu Hong, Boone Charles, Brown Grant W
Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.
EMBO J. 2003 Aug 15;22(16):4304-13. doi: 10.1093/emboj/cdg406.
Genome-wide synthetic genetic interaction screens with mutants in the mus81 and mms4 replication fork-processing genes identified a novel replication factor C (RFC) homolog, Elg1, which forms an alternative RFC complex with Rfc2-5. This complex is distinct from the DNA replication RFC, the DNA damage checkpoint RFC and the sister chromatid cohesion RFC. As expected from its genetic interactions, elg1 mutants are sensitive to DNA damage. Elg1 is redundant with Rad24 in the DNA damage response and contributes to activation of the checkpoint kinase Rad53. We find that elg1 mutants display DNA replication defects and genome instability, including increased recombination and mutation frequencies, and minichromosome maintenance defects. Mutants in elg1 show genetic interactions with pathways required for processing of stalled replication forks, and are defective in recovery from DNA damage during S phase. We propose that Elg1-RFC functions both in normal DNA replication and in the DNA damage response.
利用mus81和mms4复制叉处理基因的突变体进行全基因组合成遗传相互作用筛选，鉴定出一种新型复制因子C（RFC）同源物Elg1，它与Rfc2 - 5形成一种替代的RFC复合物。该复合物不同于DNA复制RFC、DNA损伤检查点RFC和姐妹染色单体黏连RFC。正如从其遗传相互作用所预期的那样，elg1突变体对DNA损伤敏感。在DNA损伤反应中，Elg1与Rad24功能冗余，并有助于检查点激酶Rad53的激活。我们发现elg1突变体表现出DNA复制缺陷和基因组不稳定，包括重组和突变频率增加以及微型染色体维持缺陷。elg1突变体与停滞复制叉处理所需的途径存在遗传相互作用，并且在S期从DNA损伤中恢复存在缺陷。我们提出Elg1 - RFC在正常DNA复制和DNA损伤反应中均发挥作用。
