Elg1 forms an alternative RFC complex important for DNA replication and genome integrity

被引:143
作者
Bellaoui, M
Chang, M
Ou, JW
Xu, H
Boone, C
Brown, GW [1 ]
机构
[1] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada
[2] Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5S 1A8, Canada
[3] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5G 1L6, Canada
关键词
cell cycle checkpoints; DNA damage; DNA replication; genome stability; replication factor C;
D O I
10.1093/emboj/cdg406
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:4304 / 4313
页数:10
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