The BRCT domain is a phospho-protein binding domain
The BRCT domain is a phospho-protein binding domain
复制标题
DOI：
10.1126/science.1088753
复制
发表时间：
2003-10-24
期刊：
影响因子：
56.9
通讯作者：
Chen, JJ
中科院分区：
文献类型：
--
作者：
Yu, XC;Chini, CCS;Chen, JJ
乳腺癌基因1 （BRCA1）蛋白的羧基末端结构域（BRCT）是一个进化上保守的模块，存在于从原核生物到真核生物的大量蛋白质中。尽管大多数含有BRCT结构域的蛋白质参与dna损伤检查点或dna修复途径，或两者兼而有之，但BRCT结构域的功能尚不完全清楚。我们发现BRCA1 BRCT结构域直接与磷酸化的BRCA1相关羧基末端解旋酶（BACH1）相互作用。BRCA1和磷酸化BACH1之间的这种特异性相互作用是细胞周期调控的，并且是细胞周期从G(2)期过渡到M期时DNA损伤诱导的检查点控制所必需的。此外，我们发现另外两个BRCT结构域以磷酸化依赖的方式与其各自的生理伙伴相互作用。另外13个BRCT结构域也优先结合磷酸化肽，而不是非磷酸化的对照肽。这些数据表明BRCT结构域是参与细胞周期控制的磷酸化蛋白结合结构域。
The carboxyl-terminal domain (BRCT) of the Breast Cancer Gene 1 (BRCA1) protein is an evolutionarily conserved module that exists in a large number of proteins from prokaryotes to eukaryotes. Although most BRCT domain-containing proteins participate in DNA-damage checkpoint or DNA-repair pathways, or both, the function of the BRCT domain is not fully understood. We show that the BRCA1 BRCT domain directly interacts with phosphorylated BRCA1-Associated Carboxyl-terminal Helicase (BACH1). This specific interaction between BRCA1 and phosphorylated BACH1 is cell cycle regulated and is required for DNA damage-induced checkpoint control during the transition from G(2) to M phase of the cell cycle. Further, we show that two other BRCT domains interact with their respective physiological partners in a phosphorylation-dependent manner. Thirteen additional BRCT domains also preferentially bind phospho-peptides rather than nonphosphorylated control peptides. These data imply that the BRCT domain is a phospho-protein binding domain involved in cell cycle control.