跨损伤合成途径中真核生物DNA聚合酶δ转换机制的研究进展

摘要

为维护染色体结构的完整性和遗传稳定性,除了各种分工明确的损伤修复途径外,细胞还进化出一种跨损伤修复的损伤耐受机制,涉及一种被广为深入研究的有错跨损伤合成途径,即通过低保真跨损伤合成聚合酶临时取代复制聚合酶Polδ,旁路通过受损碱基,使DNA损伤导致S-期暂停的复制叉进程得以恢复,这种复制聚合酶与跨损伤合成聚合酶之间的转换构成了有错跨损伤修复途径的核心,但对该途径聚合酶转换的激活机制存在争议.就真核生物DNA聚合酶δ的结构和功能以及在跨损伤合成途径聚合酶转换的激活机制等方面进行综述.%In order to maintain the integrity of chromosomal structure and genetic stability, in addition to those elaborate DNA damage repair mechanisms to remove DNA lesions, cells have also evolved DNA damage tolerance mechanisms to bypass damage. One exten-sively studied lesion-bypass pathway is translesion synthesis( TLS) , an error-prone repair pathway, in which replicative polymeraseδis replaced with a specialized TLS polymerase, a low fidelity enzyme, which is able to by-pass lesions, allowing stalled replication fork in S-phase to proceed. The switching between replicative and TLS polymerases is generally considered to be a core in TLS pathway. How-ever, there remains much controversy on the exact mechanism of polymerase switching. This article briefly reviewed and discussed re-searches about biological properties of eukaryotic DNA polymeraseδ, structure and function of its subunits, and activation mechanisms of polymerase switching in TLS pathway, etc.