Activation of Rad53 kinase in response to DNA damage and its effect in modulating phosphorylation of the lagging strand DNA polymerase

被引:310
作者
Pellicioli, A
Lucca, C
Liberi, G
Marini, F
Lopes, M
Plevani, P
Romano, A
Di Fiore, PP
Foiani, M
机构
[1] Univ Milan, Dipartimento Genet & Biol Microorganismi, I-20133 Milan, Italy
[2] European Inst Oncol, Milan, Italy
关键词
checkpoints; DNA damage; DNA polymerase alpha-primase; DNA replication; Rad53;
D O I
10.1093/emboj/18.22.6561
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
The Saccharomyces cerevisiae Rad53 protein kinase is required for the execution of checkpoint arrest at multiple stages of the cell cycle, We found that Rad53 autophosphorylation activity depends on in trails phosphorylation mediated by Mec1 and does not require physical association with other proteins. Uncoupling in trans phosphorylation from autophosphorylation using a rad53 kinase-defective mutant results in a dominant-negative checkpoint defect. Activation of Rad53 in response to DNA damage in G(1) requires the Rad9, Mec3, Ddc1, Rad17 and Rad24 checkpoint factors, while this dependence is greatly reduced in S phase cells. Furthermore, during recovery from checkpoint activation, Rad53 activity decreases through a process that does not require protein synthesis, We also found that Rad53 modulates the lagging strand replication apparatus by controlling phosphorylation of the DNA polymerase a-primase complex in response to intra-S DNA damage.
引用
收藏
页码:6561 / 6572
页数:12
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