Chk1 and claspin potentiate PCNA ubiquitination

被引：90

作者：

Yang, Xiaohong H. ^{[1
]}

Shiotani, Bunsyo ^{[1
]}

Classon, Marie ^{[1
]}

Zou, Lee ^{[1
,2
]}

机构：

[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA

[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

来源：

GENES & DEVELOPMENT | 2008年 / 22卷 / 09期

关键词：

Chk1; claspin; ATR; PCNA; ubiquitination; replication;

D O I：

10.1101/gad.1632808

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Chk1 is a kinase crucial for genomic integrity and an effector of ATR (ATM and Rad3-realated) in DNA damage response. Here, we show that Chk1 regulates the DNA damage-induced ubiquitination of proliferating cell nuclear antigen ( PCNA), which facilitates the continuous replication of damaged DNA. Surprisingly, this Chk1 function requires the DNA replication protein Claspin but not ATR. Claspin, which is stabilized by Chk1, regulates the binding of the ubiquitin ligase Rad18 to chromatin. Timeless, a Claspin-associating protein, is also required for efficient PCNA ubiquitination. Thus, Chk1 and the Claspin-Timeless module of replication forks not only participate in ATR signaling, but also protect stressed forks independently of ATR.

引用

页码：1147 / 1152

页数：6

共 35 条

[1] Regulation of Claspin degradation by the ubiquitin-proteo some pathway during the cell cycle and in response to ATR-dependent checkpoint activation [J].

Bennett, Lara N. ;

Clarke, Paul R. .

FEBS LETTERS, 2006, 580 (17) :4176-4181

[2] Rad18 regulates DNA polymerase κ and is required for recovery from S-phase checkpoint-mediated arrest [J].

Bi, XH ;

Barkley, LR ;

Slater, DM ;

Tateishi, S ;

Yamaizumi, M ;

Ohmori, H ;

Vaziri, C .

MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (09) :3527-3540

[3] Linking PCNA-dependent replication and ATR by human claspin [J].

Brondello, Jean-Marc ;

Ducommun, Bernard ;

Fernandez, Anne ;

Lamb, Ned J. .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 354 (04) :1028-1033

[4] Monoubiquitination of proliferating cell nuclear antigen induced by stalled replication requires uncoupling of DNA polymerase and mini-chromosome maintenance helicase activities [J].

Chang, Debbie J. ;

Lupardus, Patrick J. ;

Cimprich, Karlene A. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (43) :32081-32088

[5] Chk1 is required to maintain Claspin stability [J].

Chini, C. C. S. ;

Wood, J. ;

Chen, J. .

ONCOGENE, 2006, 25 (30) :4165-4171

[6] Repeated phosphopeptide motifs in human claspin are phosphorylated by Chk1 and mediate claspin function [J].

Chini, Claudia C. S. ;

Chen, Junjie .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (44) :33276-33282

[7] Lysine 63-polyubiquitination guards against translesion synthesis-induced mutations [J].

Chiu, Roland K. ;

Brun, Jan ;

Ramaekers, Chantal ;

Theys, Jan ;

Weng, Lin ;

Lambin, Philippe ;

Gray, Douglas A. ;

Wouters, Bradly G. .

PLOS GENETICS, 2006, 2 (07) :1070-1083

[8] Tipin and Timeless form a mutually protective complex required for genotoxic stress resistance and checkpoint function [J].

Chou, Danny M. ;

Elledge, Stephen J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (48) :18143-18147

[9] ATR and ATRIP: Partners in checkpoint signaling [J].

Cortez, D ;

Guntuku, S ;

Qin, J ;

Elledge, SJ .

SCIENCE, 2001, 294 (5547) :1713-1716

[10] Postreplication repair and PCNA modification in Schizosaccharomyces pombe [J].

Frampton, Jonathan ;

Irmisch, Anja ;

Green, Catherine M. ;

Neiss, Andrea ;

Trickey, Michelle ;

Ulrich, Helle D. ;

Furuya, Kanji ;

Watts, Felicity Z. ;

Carr, Antony M. ;

Lehmann, Alan R. .

MOLECULAR BIOLOGY OF THE CELL, 2006, 17 (07) :2976-2985

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