Extensive DNA Damage-Induced Sumoylation Contributes to Replication and Repair and Acts in Addition to the Mec1 Checkpoint

被引：164

作者：

Cremona, Catherine A. ^{[1
]}

Sarangi, Prabha ^{[1
,2
,3
,4
]}

Yang, Yan ^{[1
]}

Hang, Lisa E. ^{[1
,2
,3
,4
]}

Rahman, Sadia ^{[1
]}

Zhao, Xiaolan ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10065 USA

[2] Weill Cornell Grad Sch Med Sci, Programs Biochem, New York, NY 10065 USA

[3] Weill Cornell Grad Sch Med Sci, Cell Biol Program, New York, NY 10065 USA

[4] Weill Cornell Grad Sch Med Sci, Program Mol Biol, New York, NY 10065 USA

来源：

MOLECULAR CELL | 2012年 / 45卷 / 03期

关键词：

S-PHASE CHECKPOINT; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; HOMOLOGOUS RECOMBINATION; SUMO MODIFICATIONS; UBIQUITIN; COMPLEX; BREAKS; PHOSPHORYLATION; PROTEINS;

D O I：

10.1016/j.molcel.2011.11.028

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 cellular response to DNA damage employs multiple dynamic protein modifications to exert rapid and adaptable effects. Substantial work has detailed the roles of canonical checkpoint-mediated phosphorylation in this program. Recent studies have also implicated sumoylation in the DNA damage response; however, a systematic view of the contribution of sumoylation to replication and repair and its interplay with checkpoints is lacking. Here, using a biochemical screen in yeast, we establish that DNA damage-induced sumoylation occurs on a large scale. We identify MRX (Mre11-Rad50-Xrs2) as a positive regulator of this induction for a subset of repair targets. In addition, we find that defective sumoylation results in failure to complete replication of a damaged genome and impaired DNA end processing, highlighting the importance of the SUMO-mediated response in genome integrity. We also show that DNA damage-induced sumoylation does not require Mec1 checkpoint signaling, and the presence of both enables optimal DNA damage resistance.

引用

页码：422 / 432

页数：11

共 53 条

[1] Differential regulation of homologous recombination at DNA breaks and replication forks by the Mrc1 branch of the S-phase checkpoint [J].

Alabert, Constance ;

Bianco, Julien N. ;

Pasero, Philippe .

EMBO JOURNAL, 2009, 28 (08) :1131-1141

[2] Rad52 SUMOylation affects the efficiency of the DNA repair [J].

Altmannova, Veronika ;

Eckert-Boulet, Nadine ;

Arneric, Milica ;

Kolesar, Peter ;

Chaloupkova, Radka ;

Damborsky, Jiri ;

Sung, Patrick ;

Zhao, Xiaolan ;

Lisby, Michael ;

Krejci, Lumir .

NUCLEIC ACIDS RESEARCH, 2010, 38 (14) :4708-4721

[3] The functions of budding yeast Sae2 in the DNA damage response require Mec1- and Tel1-dependent phosphorylation [J].

Baroni, E ;

Viscardi, V ;

Cartagena-Lirola, H ;

Lucchini, G ;

Longhese, MP .

MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (10) :4151-4165

[4] Principles of ubiquitin and SUMO modifications in DNA repair [J].

Bergink, Steven ;

Jentsch, Stefan .

NATURE, 2009, 458 (7237) :461-467

[5] Ubc9-and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks [J].

Branzei, Dana ;

Sollier, Julie ;

Liberi, Giordano ;

Zhao, Xiaolan ;

Maeda, Daisuke ;

Seki, Masayuki ;

Enomoto, Takemi ;

Ohta, Kunihiro ;

Foiani, Marco .

CELL, 2006, 127 (03) :509-522

[6] Purification and identification of endogenous polySUMO conjugates [J].

Bruderer, Roland ;

Tatham, Michael H. ;

Plechanovova, Anna ;

Matic, Ivan ;

Garg, Amit K. ;

Hay, Ronald T. .

EMBO REPORTS, 2011, 12 (02) :142-148

[7] The slx5-slx8 complex affects sumoylation of DNA repair proteins and negatively regulates recombination [J].

Burgess, Rebecca C. ;

Rahman, Sadia ;

Lisby, Michael ;

Rothstein, Rodney ;

Zhao, Xiaolan .

MOLECULAR AND CELLULAR BIOLOGY, 2007, 27 (17) :6153-6162

[8] ATR homolog Mec1 promotes fork progression, thus averting breaks in replication slow zones [J].

Cha, RS ;

Kleckner, N .

SCIENCE, 2002, 297 (5581) :602-606

[9] A Proteome-wide Analysis of Kinase-Substrate Network in the DNA Damage Response [J].

Chen, Sheng-hong ;

Albuquerque, Claudio P. ;

Liang, Jason ;

Suhandynata, Raymond T. ;

Zhou, Huilin .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (17) :12803-12812

[10] Misregulation of 2μm circle copy number in a SUMO pathway mutant [J].

Chen, XL ;

Reindle, A ;

Johnson, ES .

MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (10) :4311-4320

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