Mesquita Rafael D, Woods Nicholas T, Seabra-Junior Eloy S, Monteiro Alvaro N A
Instituto Federal de Educação Ciência e Tecnologia, Rio de Janeiro, Brazil.
Genes Cancer. 2010 Nov;1(11):1140-6. doi: 10.1177/1947601910392988.
The cell's ability to sense and respond to specific stimuli is a complex system derived from precisely regulated protein-protein interactions. Some of these protein-protein interactions are mediated by the recognition of linear peptide motifs by protein modular domains. BRCT (BRCA1 C-terminal) domains and their linear motif counterparts, which contain phosphoserines, are one such pair-wise interaction system that seems to have evolved to serve as a surveillance system to monitor threats to the cell's genetic integrity. Evidence indicates that BRCT domains found in tandem can cooperate to provide sequence-specific binding of phosphorylated peptides as is the case for the breast and ovarian cancer susceptibility gene BRCA1 and the PAX transcription factor-interacting protein PAXIP1. Particular interest has been paid to tandem BRCT domains as "readers" of signaling events in the form of phosphorylated serine moieties induced by the activation of DNA damage response kinases ATM, ATR, and DNA-PK. However, given the diversity of tandem BRCT-containing proteins, questions remain as to the origin and evolution of this domain. Here, we discuss emerging views of the origin and evolving roles of tandem BRCT domain repeats in the DNA damage response.
细胞感知并响应特定刺激的能力是一个复杂的系统，它源自精确调控的蛋白质-蛋白质相互作用。其中一些蛋白质-蛋白质相互作用是由蛋白质模块化结构域识别线性肽基序介导的。BRCT（乳腺癌1号基因C末端）结构域及其含有磷酸丝氨酸的线性基序对应物就是这样一种成对相互作用系统，它似乎已经进化成为一种监测系统，用于监控对细胞遗传完整性的威胁。有证据表明，串联存在的BRCT结构域可以协同作用，实现对磷酸化肽段的序列特异性结合，乳腺癌和卵巢癌易感基因BRCA1以及与PAX转录因子相互作用的蛋白PAXIP1就是如此。串联BRCT结构域作为由DNA损伤应答激酶ATM、ATR和DNA-PK激活所诱导的磷酸化丝氨酸部分形式的信号事件的“读取器”，已经引起了特别关注。然而，鉴于含有串联BRCT结构域的蛋白质具有多样性，关于该结构域的起源和进化问题仍然存在。在这里，我们讨论了串联BRCT结构域重复序列在DNA损伤应答中的起源和不断演变的作用的新观点。
