MDC1/NFBD1: a key regulator of the DNA damage response in higher eukaryotes

被引：86

作者：

Stuck, M ^{[1
]}

Jackson, SP ^{[1
]}

机构：

[1] Univ Cambridge, Gurdon Inst Canc & Dev Biol, Wellcome Trust Canc Res UK, Dept Zool, Cambridge CB2 1QR, England

来源：

DNA REPAIR | 2004年 / 3卷 / 8-9期

关键词：

MDC1; NFBD1; DNA damage; checkpoint;

D O I：

10.1016/j.dnarep.2004.03.007

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The protein MDC1/NFBD1 contains a forkhead-associated(FHA)domain and two BRCA1 carboxyl-terminal (BRCT)domains. It interacts with several proteins involved in DNA damage repair and checkpoint signal I m,, and is phosphorylated in response to DNA damage and during mitosis. Upon treatment of cultured human cells with DNA damaging agents, MDC1/NFBD1 translocates to sites of DNA lesions, where it collaborates with other proteins and with phosphorylated histone H2AX to mediate the accumulation of checkpoint and repair factors into nuclear foci. Down-regulation of MDC1/NFBD1 expression levels by small interfering RNA (siRNA) renders cells hyper-sensitive to DNA damaging agents and leads to defects in cell cycle checkpoint activation and apoptosis. Thus, MDC1/NFBD1 appears to be a key regulator of the DNA damage response in mammalian cells. (C) 2004 Elsevier B.V. All rights reserved.

引用

页码：953 / 957

页数：5

共 43 条

[1] DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation [J].