Homo-oligomerization is the essential function of the tandem BRCT domains in the checkpoint protein Crb2
Homo-oligomerization is the essential function of the tandem BRCT domains in the checkpoint protein Crb2
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DOI：
10.1074/jbc.m403326200
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发表时间：
2004-09-10
影响因子：
4.8
通讯作者：
Russell, P
中科院分区：
文献类型：
--
作者：
Du, LL;Moser, BA;Russell, P
BRCT(BRCA1 C末端)结构域在酿酒酵母RAD9、人53BP1和BRCA1等参与DNA损伤反应的蛋白质中经常以串联重复的形式存在。串联的BRCT结构域介导蛋白质-蛋白质和蛋白质-DNA的相互作用。然而，这些相互作用的功能意义在很大程度上是未知的。在这里，我们报道了裂殖酵母Pombe检查点蛋白Crb2通过其串联的BRCT结构域的寡聚。没有BRCT结构域的截短的Crb2在DNA损伤检查点信号中是有缺陷的。然而，添加两个异源二聚基序中的任何一个，都可以在很大程度上恢复没有BRCT结构域的截断的Crb2的功能。用二聚化基序替换Crb2BRCT结构域也使细胞对过度表达Crb2BRCT结构域的显性负面效应产生抵抗。这些结果表明，串联的BRCT结构域的关键功能是寡聚Crb2。
BRCT (BRCA1 C terminus) domains are frequently found as a tandem repeat in proteins involved in DNA damage responses, such as Saccharomyces cerevisiae Rad9, human 53BP1 and BRCA1. Tandem BRCT domains mediate protein-protein and protein-DNA interactions. However, the functional significance of these interactions is largely unknown. Here we report the oligomerization of Schizosaccharomyces pombe checkpoint protein Crb2 through its tandem BRCT domains. Truncated Crb2 without BRCT domains is defective in DNA damage checkpoint signaling. However, addition of either of two heterologous dimerization motifs largely restores the functions of truncated Crb2 without BRCT domains. Replacement of Crb2 BRCT domains with a dimerization motif also renders cells resistant to the dominant negative effect of overexpressing Crb2 BRCT domains. These results demonstrate that the crucial function of the tandem BRCT domains is to oligomerize Crb2.