The set1Δ mutation unveils a novel signaling pathway relayed by the Rad53-dependent hyperphosphorylation of replication protein A that leads to transcriptional activation of repair genes

被引:43
作者
Schramke, V
Neecke, H
Brevet, V
Corda, Y
Lucchini, G
Longhese, MP
Gilson, E
Géli, V
机构
[1] CNRS, IBSM, Lab Ingn Syst Macromol, F-13402 Marseille 20, France
[2] Univ Milan, I-20126 Milan, Italy
[3] CNRS, LBCM, F-69364 Lyon, France
关键词
SET domain; RPA; phosphorylation; checkpoint; DNA repair; telomere; gene silencing;
D O I
10.1101/gad.193901
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
SET domain proteins are present in chromosomal proteins involved in epigenetic control of transcription. The yeast SET domain protein Set1p regulates chromatin structure, DNA repair, and telomeric functions. We investigated the mechanism by which the absence of Set1p increases DNA repair capacities of checkpoint mutants. We show that deletion of SETI induces a response relayed by the signaling kinase Rad53p that leads to the MEC1/TEL1-independent hyperphosphorylation of replication protein A middle subunit (Rfa2p). Consequently, the binding of Rfa2p to upstream repressing sequences (URS) of repair genes is decreased, thereby lending to their derepression. Our results correlate the set1 Delta -dependent phosphorylation of Rfa2p with the transcriptional induction of repair genes. Moreover, we show that the deletion of the amino-terminal region of Rfa2p suppresses the sensitivity to ultraviolet radiation of a mec3 Delta checkpoint mutant, abolishes the URS-mediated repression, and increases the expression of repair genes. This work provides an additional link for the role of Rfa2p in the regulation of the repair capacity of the cell and reveals a role for the phosphorylation of Rfa2p and unveils unsuspected connections between chromatin, signaling pathways, telomeres, and DNA repair.
引用
收藏
页码:1845 / 1858
页数:14
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