Stem Cell Epigenetics Laboratory, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
Cell Cycle. 2011 May 1;10(9):1356-62. doi: 10.4161/cc.10.9.15442.
In response to DNA damaging agents and endogenous DNA lesions, human cells activate signaling cascades and repair mechanisms to help maintain genomic integrity. Phosphorylation plays a major role in DNA damage signaling, and the role of Ser/Thr kinases, including ATM, ATR, CHK1, CHK2 and DNA-PK, is particularly well documented. While these kinases have taken the center stage in DNA damage signaling until now, a role for Ser/Thr phosphatases is emerging, including Protein Phosphatase 1 (PP1). PP1 substrate specificity is regulated by its binding to a large number of different targeting subunits, and several of these have recently been identified as regulators of DNA damage responses. Here we review recent progress regarding the involvement of PP1 and its binding partners in DNA damage signaling.
为了应对 DNA 损伤剂和内源性 DNA 损伤，人类细胞激活信号级联和修复机制，以帮助维持基因组完整性。磷酸化在 DNA 损伤信号中起着主要作用，丝氨酸/苏氨酸激酶（包括 ATM、ATR、CHK1、CHK2 和 DNA-PK）的作用尤其有充分的记录。虽然这些激酶在 DNA 损伤信号中一直占据中心舞台，但丝氨酸/苏氨酸磷酸酶的作用正在显现，包括蛋白磷酸酶 1（PP1）。PP1 的底物特异性受其与大量不同靶向亚基结合的调节，其中一些最近被确定为 DNA 损伤反应的调节剂。在这里，我们综述了 PP1 及其结合伙伴参与 DNA 损伤信号的最新进展。
