MDC1 collaborates with TopBP1 in DNA replication checkpoint control

被引：80

作者：

Wang, Jiadong ^{[1
]}

Gong, Zihua ^{[1
]}

Chen, Junjie ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA

来源：

JOURNAL OF CELL BIOLOGY | 2011年 / 193卷 / 02期

基金：

美国国家卫生研究院;

关键词：

DOUBLE-STRAND BREAKS; S-PHASE CHECKPOINT; MRE11-RAD50-NBS1; COMPLEX; CONTAINING PROTEIN; GENOME INTEGRITY; BUDDING YEAST; DAMAGE; ATR; CHROMATIN; PHOSPHORYLATION;

D O I：

10.1083/jcb.201010026

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Human TopBP1 is a major player in the control of the DNA replication checkpoint. In this study, we identified MDC1, a key checkpoint protein involved in the cellular response to DNA double-strand breaks, as a TopBP1-associated protein. The specific TopBP1-MDC1 interaction is mediated by the fifth BRCT domain of TopBP1 and the Ser-Asp-Thr (SDT) repeats of MDC1. In addition, we demonstrated that TopBP1 accumulation at stalled replication forks is promoted by the H2AX/MDC1 signaling cascade. Moreover, MDC1 is important for ATR-dependent Chk1 activation in response to replication stress. Collectively, our data suggest that MDC1 facilitates several important steps in both cellular DNA damage response and the DNA replication checkpoint.

引用

页码：267 / 273

页数：7

共 34 条

[1] How ATR turns on: TopBP1 goes on ATRIP with ATR [J].

Burrows, Anna E. ;

Elledge, Stephen J. .

GENES & DEVELOPMENT, 2008, 22 (11) :1416-1421

[2] TopBP1 functions with 53BP1 in the G1 DNA damage checkpoint [J].

Cescutti, Rachele ;

Negrini, Simona ;

Kohzaki, Masaoki ;

Halazonetis, Thanos D. .

EMBO JOURNAL, 2010, 29 (21) :3723-3732

[3] Phospho-dependent interactions between NBS1 and MDC1 mediate chromatin retention of the MRN complex at sites of DNA damage [J].

Chapman, J. Ross ;

Jackson, Stephen P. .

EMBO REPORTS, 2008, 9 (08) :795-801

[4] ATR: an essential regulator of genome integrity [J].

Cimprich, Karlene A. ;

Cortez, David .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2008, 9 (08) :616-627

[5] The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1 [J].

Delacroix, Sinny ;

Wagner, Jill M. ;

Kobayashi, Masahiko ;

Yamamoto, Ken-ichi ;

Karnitz, Larry M. .

GENES & DEVELOPMENT, 2007, 21 (12) :1472-1477

[6] BACH1/FANCJ Acts with TopBP1 and Participates Early in DNA Replication Checkpoint Control [J].

Gong, Zihua ;

Kim, Ja-Eun ;

Leung, Charles Chung Yun ;

Glover, J. N. Mark ;

Chen, Junjie .

MOLECULAR CELL, 2010, 37 (03) :438-446

[7] THE BIPHENYL POLYCHLORINATED BIPHENYL-DEGRADATION LOCUS (BPH) OF PSEUDOMONAS SP LB400 ENCODES 4 ADDITIONAL METABOLIC ENZYMES [J].

HOFER, B ;

BACKHAUS, S ;

TIMMIS, KN .

GENE, 1994, 144 (01) :9-16

[8] RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly [J].

Huen, Michael S. Y. ;

Grant, Robert ;

Manke, Isaac ;

Minn, Kay ;

Yu, Xiaochun ;

Yaffe, Michael B. ;

Chen, Junjie .

CELL, 2007, 131 (05) :901-914

[9] MDC1: The art of keeping things in focus [J].

Jungmichel, Stephanie ;

Stucki, Manuel .

CHROMOSOMA, 2010, 119 (04) :337-349

[10] Human TopBP1 ensures genome integrity during normal S phase [J].

Kim, JE ;

McAvoy, SA ;

Smith, DI ;

Chen, JJ .

MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (24) :10907-10915

← 1 2 3 4 →