Summers K C, Shen F, Sierra Potchanant E A, Phipps E A, Hickey R J, Malkas L H
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Int J Proteomics. 2011;2011:373816. doi: 10.1155/2011/373816. Epub 2011 May 18.
Repair of double-stranded breaks (DSBs) is vital to maintaining genomic stability. In mammalian cells, DSBs are resolved in one of the following complex repair pathways: nonhomologous end-joining (NHEJ), homologous recombination (HR), or the inclusive DNA damage response (DDR). These repair pathways rely on factors that utilize reversible phosphorylation of proteins as molecular switches to regulate DNA repair. Many of these molecular switches overlap and play key roles in multiple pathways. For example, the NHEJ pathway and the DDR both utilize DNA-PK phosphorylation, whereas the HR pathway mediates repair with phosphorylation of RPA2, BRCA1, and BRCA2. Also, the DDR pathway utilizes the kinases ATM and ATR, as well as the phosphorylation of H2AX and MDC1. Together, these molecular switches regulate repair of DSBs by aiding in DSB recognition, pathway initiation, recruitment of repair factors, and the maintenance of repair mechanisms.
双链断裂（DSB）的修复对于维持基因组稳定性至关重要。在哺乳动物细胞中，DSB通过以下复杂修复途径之一进行修复：非同源末端连接（NHEJ）、同源重组（HR）或包容性DNA损伤反应（DDR）。这些修复途径依赖于利用蛋白质可逆磷酸化作为分子开关来调节DNA修复的因子。这些分子开关中的许多相互重叠，并在多种途径中发挥关键作用。例如，NHEJ途径和DDR都利用DNA-PK磷酸化，而HR途径通过RPA2、BRCA1和BRCA2的磷酸化介导修复。此外，DDR途径利用激酶ATM和ATR，以及H2AX和MDC1的磷酸化。这些分子开关共同通过协助DSB识别、途径启动、修复因子募集和修复机制的维持来调节DSB的修复。
