School of Molecular Biosciences, Washington State University, Pullman, Washington, USA.
Environ Mol Mutagen. 2010 Jul;51(6):582-603. doi: 10.1002/em.20577.
Homologous recombination repair (HRR) encompasses mechanisms that employ homologous DNA sequences as templates for repair or tolerance of a wide range of DNA lesions that inhibit DNA replication in S phase. Arguably the most imposing of these DNA lesions is that of the interstrand crosslink (ICL), consisting of a covalently attached chemical bridge between opposing DNA strands. ICL repair requires the coordinated activities of HRR and a number of proteins from other DNA repair and damage response systems, including nucleotide excision repair, base excision repair, mismatch repair, and translesion DNA synthesis (TLS). Interestingly, different organisms favor alternative methods of HRR in the ICL repair process. E. coli perform ICL repair using a homology-driven damage bypass mechanism analogous to daughter strand gap repair. Eukaryotes from yeast to humans initiate ICL repair primarily during DNA replication, relying on HRR activity to restart broken replication forks associated with double-strand break intermediates induced by nucleolytic activities of other excision repair factors. Higher eukaryotes also employ several additional factors, including members of the Fanconi anemia damage-response network, which further promote replication-associated ICL repair through the activation and coordination of various DNA excision repair, TLS, and HRR proteins. This review focuses on the proteins and general mechanisms of HRR associated with ICL repair in different model organisms.
同源重组修复 (HRR) 包括利用同源 DNA 序列作为模板进行修复或耐受广泛的 DNA 损伤的机制，这些损伤会抑制 S 期的 DNA 复制。这些 DNA 损伤中最引人注目的可能是链间交联 (ICL)，它由相反 DNA 链之间共价连接的化学桥组成。ICL 修复需要 HRR 的协调活动以及来自其他 DNA 修复和损伤反应系统的许多蛋白质的参与，包括核苷酸切除修复、碱基切除修复、错配修复和跨损伤 DNA 合成 (TLS)。有趣的是，不同的生物体在 ICL 修复过程中倾向于采用替代的 HRR 方法。大肠杆菌使用类似于子链缺口修复的同源驱动损伤旁路机制来进行 ICL 修复。从酵母到人等真核生物主要在 DNA 复制期间启动 ICL 修复，依赖 HRR 活性来重新启动与其他切除修复因子的核酶活性诱导的双链断裂中间体相关的断裂复制叉。高等真核生物还使用几种额外的因子，包括范可尼贫血损伤反应网络的成员，它们通过激活和协调各种 DNA 切除修复、TLS 和 HRR 蛋白来进一步促进与复制相关的 ICL 修复。这篇综述重点介绍了与不同模式生物的 ICL 修复相关的 HRR 蛋白和一般机制。
