《生命科学》 2014, 26(11): 1143-1156

受PCNA翻译后修饰调控的DNA损伤耐受机制

秦周帅，张传林，萧　伟*

(首都师范大学生命科学学院，北京 100048)

摘　要：摘　要：为了应对DNA 损伤复制阻滞，增殖细胞核抗原(proliferating cell nuclear antigen， PCNA)164 位点的赖氨酸残基能够发生一系列的泛素化修饰并介导两种不用的损伤耐受机制，即DNA 跨损伤合成(TLS) 和无错耐受通路。目前，单泛素化的PCNA 介导DNA 跨损伤合成通路，而多泛素化的PCNA 介导无错耐受通路这一观点已被普遍认可。另外，PCNA 的164 位点还能被泛素类似物小蛋白(SUMO) 修饰，从而抑制DNA 双链断裂重组。总结PCNA 的翻译后修饰及其在DNA 损伤应答过程中的作用机制，有助于我们了解PCNA 在DNA 损伤耐受机制中的中心作用。重点总结PCNA 的翻译后修饰如何调控真核生物DNA 损伤应答的不同途径。

DNA damage tolerance controlled by PCNA post-translational modifications

QIN Zhou-Shuai， ZHANG Chuan-Lin， XIAO Wei*

(College of Life Sciences， Capital Normal University， Beijing 100048， China)

Abstract: Abstract: In response to replication-blocking lesions， proliferating cell nuclear antigen (PCNA) can be sequentially ubiquitinated at the K164 residue， leading to two modes of DNA-damage tolerance (DDT)， namely， translesion DNA synthesis (TLS) and error-free lesion bypass. It is generally believed that monoubiquitinated PCNA promotes TLS， whereas polyubiquitinated PCNA mediates an error-free mode of lesion bypass. In addition， PCNA can also be sumoylated at the same K164 residue to inhibit double-strand break recombination. Understanding PCNA posttranslational modifications and their implications reveals the central role of PCNA in regulating DDT. In this review， we describe how PCNA post‑translational modifications mediate different mechanisms of DDT in response to lethal DNA damage in eukaryotes， from yeast to human.