DNA损伤修复机制——解读2015年诺贝尔化学奖

Tomas Lindahl, Paul Modrich和Aziz Sancar三位科学家因发现“DNA损伤修复机制”获得了2015年诺贝尔化学奖．Lindahl首次发现Escherichia Coli中参与碱基切除修复的第一个蛋白质--尿嘧啶 DNA糖基化酶（UNG）; Modrich重建了错配修复的体外系统，从大肠杆菌到哺乳动物深入探究了错配修复的机制; Sancar利用纯化的UvrA、UvrB、UvrC重建了核苷酸切除修复的关键步骤，阐述了核苷酸切除修复的分子机制．DNA损伤是由生物所处体外环境和体内因素共同导致的，面对不同种类的损伤，机体启动多种不同的修复机制修复损伤，保护基因组稳定性．这些修复机制包括：光修复(light repairing)；核苷酸切除修复（nucleotide excision repair, NER）；碱基切除修复（base excision repair, BER）；错配修复（mismatch repair, MMR）；以及DNA双链断裂修复（DNA double strand breaks repair, DSBR）．其中DNA双链断裂修复又分同源重组（homologous recombination, HR）和非同源末端连接（non homologous end joining, NHEJ）两种方式．本文将对上述几种修复的机制进行总结与讨论．

The Repair Mechanism for DNA Damage Understanding The 2015 Nobel Prize in Chemistry

The Royal Swedish Academy of Sciences has awarded the 2015 Nobel Prize in Chemistry to Tomas Lindahl, Paul Modrich and Aziz Sancar for their “mechanistic studies of DNA repair”. Lindahl identified a complete new group of DNA glycosylase and described their role in base excision repair; Modrich reconstituted DNA mismatch repair in a defined in vitro system and found the mechanism of mismatch repair from bacterial to eukaryotic cells; Sancar used the purified UvrA, UvrB, and UvrC proteins to reconstitute essential steps in the NER pathways and described the molecular mechanism of nucleotide excision repair. Cells from all living organisms are constantly being exposed to the factors of environment or endogenous metabolic products, which causes a range of DNA damages. To protect genome stability, an intricate DNA repair systems have evolved in evolution. The choice of repair mechanism is largely defined by the type of damage, but other factors such as the stage of the cell cycle also have a role. The major repair mechanisms include light repairing, nucleotide excision repair, base excision repair, mismatch repair and double strand breaks repair. The mechanisms that cope with DSBs are homologous recombination and non homologous end joining. This article reviews and discusses current understanding of DNA repair system for further studies.