期刊
JOURNAL OF CELL BIOLOGY
卷 158, 期 5, 页码 863-872出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200204127
关键词
cell cycle; Rad 17; DNA damage; DNA replication; S phase
类别
资金
- NIGMS NIH HHS [T32GM07598, T32 GM007598] Funding Source: Medline
Alkylating agents, such as methyl methanesulfonate (MMS), damage DNA and activate the DNA damage checkpoint. Although many of the checkpoint proteins that transduce damage signals have been identified and characterized, the mechanism that senses the damage and activates the checkpoint is not yet understood. To address this issue for alkylation damage, we have reconstituted the checkpoint response to MMS in Xenopus egg extracts. Using four different indicators for checkpoint activation (delay on entrance into mitosis, slowing of DNA replication, phosphorylation of the Chk1 protein, and physical association of the Rad17 checkpoint protein with damaged DNA), we report that MMS-induced checkpoint activation is dependent upon entrance into S phase. Additionally, we show that the replication of damaged double-stranded DNA, and not replication of damaged single-stranded DNA, is the molecular event that activates the checkpoint. Therefore, these data provide direct evidence that replication forks are an obligate intermediate in the activation of the DNA damage checkpoint.
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