RAD18在DNA损伤的复制后修复以及同源重组修复过程中起着重要作用。在本研究论文中，黄俊课题组发现蛋白BRCTx通过其N端BRCT结构域与RAD18相互作用，而且它们的相互作用依赖于RAD18Ser442和Ser444位点的磷酸化。实验表明BRCTx不影响细胞受UV损伤后RAD18对PCNA的单泛素化，也不影响RAD18参与DNA同源重组修复的功能，然而，BRCTx与RAD18的相互作用对于细胞在UV照射后的存活起着重要作用。这一研究结果表明，RAD18除了通过介导PCNA的泛素化参与复制后修复机制外，细胞内还存在着一条通过RAD18-BRCTx相互作用而进行的复制后修复机制。浙江大学生命科学研究院的刘婷博士和研究生陈红霞分别是这篇文章的第一和第二作者。
RAD18-BRCTx interaction is required for efficient repair of UV-induced DNA damage.
Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Abstract
BRCA1 carboxyl-terminal (BRCT) motifs are present in a number of proteins involved in DNA repair and/or DNA damage signaling pathways. The BRCT domain-containing protein BRCTx has been shown to interact physically with RAD18, an E3 ligase involved in postreplication repair and homologous recombination repair. However, the physiological relevance of the interaction between RAD18 and BRCTx is largely unknown. In this study, we showed that RAD18 interacts with BRCTx in a phosphorylation-dependent manner and that this interaction, mediated via highly conserved serine residues on the RAD18 C terminus, is required for BRCTx accumulation at DNA damage sites. Furthermore, we uncovered critical roles of the RAD18-BRCTx module in UV-induced DNA damage repair but not PCNA mono-ubiquitination or homologous recombination. Thus, our results suggest that RAD18 has an additional function in the surveillance of the UV-induced DNA damage response signal.
原文链接：http://www.sciencedirect.com/science/article/pii/S1568786411003077
