Helt Christopher E, Wang Wensheng, Keng Peter C, Bambara Robert A
Department of Radiation Oncology, School of Medicine and Dentistry, The University of Rochester, Rochester, New York 14642, USA.
Cell Cycle. 2005 Apr;4(4):529-32. doi: 10.4161/cc.4.4.1598. Epub 2005 Apr 10.
The toroidal Rad9-Rad1-Hus1 checkpoint complex (9-1-1) is structurally similar to the proliferating cell nuclear antigen (PCNA), which serves as a sliding clamp platform for DNA replication and repair. 9-1-1 has been characterized as a sensor of DNA damage that functions in concert with the checkpoint control proteins ATM and ATR. However, recent data suggest that the 9-1-1 complex and its individual Rad9 component serve different and multiple functions in cells by sensing DNA damage, stimulating apoptosis, and regulating gene transcription. Recently it was reported that 9-1-1 interacts with and/or stimulates components of the base excision repair (BER) pathway including the S. pombe MutY homolog (MYH), human polymerase beta (Polbeta), and flap endonuclease 1 (FEN1). Furthermore, preliminary results indicate a stimulation of DNA ligase I. In this review, the likely direct participation of 9-1-1 in DNA repair is discussed.
环形的Rad9-Rad1-Hus1检查点复合物(9-1-1)在结构上与增殖细胞核抗原(PCNA)相似,PCNA作为DNA复制和修复的滑动夹平台。9-1-1已被表征为一种DNA损伤传感器,与检查点控制蛋白ATM和ATR协同发挥作用。然而,最近的数据表明,9-1-1复合物及其单个Rad9组分通过感知DNA损伤、刺激细胞凋亡和调节基因转录,在细胞中发挥不同的多种功能。最近有报道称,9-1-1与碱基切除修复(BER)途径的组分相互作用和/或刺激这些组分,包括粟酒裂殖酵母MutY同源物(MYH)、人聚合酶β(Polβ)和瓣状核酸内切酶1(FEN1)。此外,初步结果表明对DNA连接酶I有刺激作用。在这篇综述中,将讨论9-1-1可能直接参与DNA修复的情况。