A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway

被引:63
作者
Marchetti, MA
Kumar, S
Hartsuiker, E
Maftahi, M
Carr, AM
Freyer, GA
Burhans, WC
Huberman, JA
机构
[1] Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA
[2] Univ Sussex, Genome Damage & Stabil Ctr, Sch Biol Sci, Brighton BN1 9RR, E Sussex, England
[3] Columbia Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY 10032 USA
关键词
D O I
10.1073/pnas.112702399
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The eukaryotic intra-S-phase checkpoint, which slows DNA synthesis in response to DNA damage, is poorly understood. Is DNA damage recognized directly, or indirectly through its effects on replication forks? Is the slowing of S phase in part because of competition between DNA synthesis and recombination/repair processes? The results of our genetic analyses of the intra-S-phase checkpoint in the fission yeast, Schizosaccharomyces pombe, suggest that the slowing of S phase depends weakly on the helicases Rqh1 and Srs2 but not on other recombination/repair pathways. The slowing of S phase depends strongly on the six checkpoint-Rad proteins, on Cds1, and on Rad4/Cut5 (similar to budding yeast Dpb11, which interacts with DNA polymerase F) but not on Rhp9 (similar to budding yeast Rad9, necessary for direct damage recognition). These results suggest that, in fission yeast, the signal activating the intra-S-phase checkpoint is generated only when replication forks encounter DNA damage.
引用
收藏
页码:7472 / 7477
页数:6
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