Vaisman Alexandra, Woodgate Roger
a Laboratory of Genomic Integrity , National Institute of Child Health and Human Development, National Institutes of Health , Bethesda , MD , USA.
Crit Rev Biochem Mol Biol. 2017 Jun;52(3):274-303. doi: 10.1080/10409238.2017.1291576. Epub 2017 Mar 9.
Life as we know it, simply would not exist without DNA replication. All living organisms utilize a complex machinery to duplicate their genomes and the central role in this machinery belongs to replicative DNA polymerases, enzymes that are specifically designed to copy DNA. "Hassle-free" DNA duplication exists only in an ideal world, while in real life, it is constantly threatened by a myriad of diverse challenges. Among the most pressing obstacles that replicative polymerases often cannot overcome by themselves are lesions that distort the structure of DNA. Despite elaborate systems that cells utilize to cleanse their genomes of damaged DNA, repair is often incomplete. The persistence of DNA lesions obstructing the cellular replicases can have deleterious consequences. One of the mechanisms allowing cells to complete replication is "Translesion DNA Synthesis (TLS)". TLS is intrinsically error-prone, but apparently, the potential downside of increased mutagenesis is a healthier outcome for the cell than incomplete replication. Although most of the currently identified eukaryotic DNA polymerases have been implicated in TLS, the best characterized are those belonging to the "Y-family" of DNA polymerases (pols η, ι, κ and Rev1), which are thought to play major roles in the TLS of persisting DNA lesions in coordination with the B-family polymerase, pol ζ. In this review, we summarize the unique features of these DNA polymerases by mainly focusing on their biochemical and structural characteristics, as well as potential protein-protein interactions with other critical factors affecting TLS regulation.
我们所知的生命，如果没有DNA复制就根本不会存在。所有生物都利用一套复杂的机制来复制它们的基因组，而在这套机制中起核心作用的是复制性DNA聚合酶，即专门用于复制DNA的酶。“轻松无忧”的DNA复制只存在于理想世界中，而在现实生活中，它不断受到各种各样挑战的威胁。复制性聚合酶自身常常无法克服的最紧迫障碍之一是扭曲DNA结构的损伤。尽管细胞利用精心设计的系统来清除基因组中的受损DNA，但修复往往并不完全。阻碍细胞复制酶的DNA损伤持续存在可能会产生有害后果。细胞完成复制的一种机制是“跨损伤DNA合成（TLS）”。TLS本质上容易出错，但显然，增加诱变的潜在不利影响对细胞来说比不完全复制是更有利的结果。虽然目前已鉴定出的大多数真核生物DNA聚合酶都与TLS有关，但特征最明确的是那些属于DNA聚合酶“Y家族”（聚合酶η、ι、κ和Rev1）的成员，它们被认为在与B家族聚合酶pol ζ协同作用下，在持续存在的DNA损伤的TLS中起主要作用。在这篇综述中，我们主要通过关注它们的生化和结构特征，以及与影响TLS调控的其他关键因子的潜在蛋白质 - 蛋白质相互作用，来总结这些DNA聚合酶的独特特性。
