The role of small ubiquitin-like modifier (SUMO) in DNA end resection

双链断裂（DSB）是最危险的DNA损伤之一，据估计在原代人或小鼠成纤维细胞中以每天每个细胞10个的速率发生。这些天然存在的DSB是在停滞的DNA复制叉、跨切口复制、内源性来源的活性氧物质或DNA内切酶的不合时宜的作用崩溃时产生的。DSB主要通过非同源末端连接（NHEJ）和同源重组（HR）修复。NHEJ是主要途径，并在整个细胞周期中使用，而HR在S/G2期活跃，其中姐妹染色单体可用作修复模板。DSB修复途径选择的调节对我们的细胞非常重要，因为DSB修复途径选择中的错误可以产生基因重排，并且错误的DSB修复通常产生杀死细胞的异常染色体结构。NHEJ仅在最低程度加工的DNA末端上有活性;它被DNA末端切除抑制，DNA末端切除是5 '-3'核酸降解产生单链DNA（ssDNA）的过程。3 '-ssDNA突出端立即被复制蛋白A（RPA）蛋白复合物（由约70、32和14 kDa的亚基组成，分别称为RPA 70、RPA 32和RPA 14）包被以进行保护。RPA包被的ssDNA是所有HR子途径的必需中间体。CtBP相互作用蛋白（CtIP）是控制DNA末端切除的关键DNA内切酶。CtIP通过多种翻译后修饰（PTM）靶向，包括磷酸化、泛素化、乙酰化和其他鲜为人知的修饰。

Double-strand breaks (DSBs), which are among the most dangerous DNA lesions, are estimated to occur at a rate of ten per cell per day in primary human or mouse fibroblasts. These naturally occurring DSBs are generated upon collapse of stalled DNA replication forks, replication across nicks, reactive oxygen species of endogenous origin or the untimely action of DNA endonucleases. DSBs are mainly repaired by non-homologous end joining (NHEJ) and homologous recombination (HR). NHEJ is the primary pathway and is used throughout the cell cycle, while HR is active in S/G2 phases where sister chromatids are available as repair templates. The regulation of DSB repair pathway choice is of great importance to our cells since errors in the choice of DSB repair pathway can create gene rearrangements and faulty DSB repair often generates aberrant chromosomal structures that kill cells. NHEJ is active only on minimally processed DNA ends; it is inhibited by DNA end resection, the process by which 5’-3’ nucleolytic degradation generates single-stranded DNA (ssDNA). The 3'-ssDNA overhangs are immediately coated by the Replication Protein A (RPA) protein complexes (composed of subunits of ~70, 32, and 14 kDa, referred as to RPA70, RPA32, and RPA14, respectively) for protection. The RPA-coated ssDNA is an essential intermediate of all HR sub-pathways. CtBP-interacting protein (CtIP) is a key DNA endonuclease controlling DNA end resection. CtIP is targeted by multiple posttranslational modifications (PTMs) including phosphorylation, ubiquityation, acetylation and other less known modifications.