过程性
DNA聚合酶
DNA复制
生物
DNA修复
DNA损伤
遗传学
DNA聚合酶δ
细胞生物学
蛋白质亚单位
聚合酶
真核细胞DNA复制
DNA
基因
聚合酶链反应
逆转录酶
作者
Qian Zhang,Huiqing Chen,Chen Yan,Yajing Zhou
出处
期刊:Current Protein & Peptide Science
[Bentham Science]
日期:2016-10-04
卷期号:17 (8): 746-755
被引量:4
标识
DOI:10.2174/1389203717666160226145006
摘要
Among three major replicative DNA polymerases of the B-family, Pol α, Pol δ and Pol ε, Pol δ plays an essential role in chromosomal DNA replication and is also involved in various DNA repair processes in eukaryotes. Human Pol δ is commonly viewed as a heterotetrameric complex, consisting of the catalytic subunit p125 and second subunit p50, together with two additional accessory subunits, p68 and p12. A growing body of research has shown that the latter subunits play a critical role in the regulation of Pol δ functions. The formation of a new form of Pol δ, heterotrimer Pol δ3, is found by virtue of the depletion of p12 through the ubiquitin-proteasome pathway in response to DNA damages that are trigged by UV irradiation, alkylating agents, oxidative and replication stresses. Pol δ3 exhibits significant differences in properties to its progenitor with a major impact on cellular processes in genomic surveillance, DNA replication and DNA repair. Our recent studies indicate that there exists an alternative pathway for Pol δ3 formation by calpain-mediated proteolysis of p12 in a calcium-triggered apoptosis in living cells. In this article, we review and discuss the recent advances from our group and others in the studies of human Pol δ with an emphasis on the generation of its multiple forms by reconstitution and subsequent alternations in enzymatic properties, the multiple pathways of the Pol δ3 formation in living cells, and the phylogenetic analysis of the evolutionary history on POLD4 gene that is for the p12 subunit.
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