期刊
CELL CYCLE
卷 6, 期 10, 页码 1157-1160出版社
LANDES BIOSCIENCE
DOI: 10.4161/cc.6.10.4221
关键词
DNA replication; DNA damage; cell cycle checkpoint; clamp; checkpoint kinase
类别
资金
- NIGMS NIH HHS [R01 GM032431, GM032431] Funding Source: Medline
The yeast checkpoint protein kinase Mec1, the ortholog of human ATR, is the essential upstream regulator of the cell cycle checkpoint in response to DNA damage and to stalling of DNA replication forks. The activity of Mec1/ATR is not directly regulated by the DNA substrates that signal checkpoint activation. Rather the signal appears to be transduced to Mec1 by factors that interact with the signaling DNA substrates. One of these factors, the DNA damage checkpoint clamp Rad17-Mec3-Ddc1 (human 9 - 1 - 1) is loaded onto gapped DNA resulting from the partial repair of DNA damage, and the Ddc1 subunit of this complex activates Mec1. In vertebrate cells, the TopBP1 protein (Cut5 in S. pombe and Dpb11 in S. cervisiae) that is also required for establishment of the replication fork, functions during replication fork dysfunction to activate ATR. Both mechanisms of activation generally upregulate the kinase activity towards all downstream targets.
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