PrimPol, an archaic primase/polymerase operating in human cells.

PrimPol, an archaic primase/polymerase operating in human cells.
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PRIMPOL,一种在人类细胞中运行的古代起点酶/聚合酶。

DOI:
10.1016/j.molcel.2013.09.025
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发表时间:
2013-11-21
期刊:
影响因子:
16
通讯作者:
Blanco L
Blanco L
中科院分区:
生物学1区
文献类型:
--
作者:
García-Gómez S;Reyes A;Martínez-Jiménez MI;Chocrón ES;Mourón S;Terrados G;Powell C;Salido E;Méndez J;Holt IJ;Blanco L

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我们描述了人类细胞中的第二种引发酶PrimPol,它具有用脱氧核苷酸启动DNA链的能力,而不像常规的引发酶,它只使用核糖核苷酸。此外,PrimPol也是一种DNA聚合酶,专门用于绕过DNA中最常见的氧化损伤,如脱碱基位点和8-氧代鸟嘌呤。亚细胞分级分离和免疫检测研究表明,PrimPol存在于细胞核和线粒体DNA区室。PrimPol活性在来自人和小鼠细胞的线粒体裂解物中可检测到,但在来自PRIMPOL敲除小鼠的线粒体中不存在。人类和小鼠细胞中的PRIMPOL基因沉默或消融损害线粒体DNA复制。基于与复制型DNA聚合酶Polγ和Polε观察到的协同作用,提出PrimPol通过作为跨损伤DNA聚合酶或作为在线粒体和核DNA复制期间阻断合成的损伤下游重新启动的特异性DNA引发酶来促进复制叉进展。PrimPol是第二种能够用dNTP启动DNA链的人引发酶PrimPol作为耐受AP位点和8 oxoG损伤的DNA聚合酶的鉴定PrimPol位于DNA区室、线粒体和细胞核中PRIMPOL基因沉默影响mtDNA复制
We describe a second primase in human cells, PrimPol, which has the ability to start DNA chains with deoxynucleotides unlike regular primases, which use exclusively ribonucleotides. Moreover, PrimPol is also a DNA polymerase tailored to bypass the most common oxidative lesions in DNA, such as abasic sites and 8-oxoguanine. Subcellular fractionation and immunodetection studies indicated that PrimPol is present in both nuclear and mitochondrial DNA compartments. PrimPol activity is detectable in mitochondrial lysates from human and mouse cells but is absent from mitochondria derived from PRIMPOL knockout mice. PRIMPOL gene silencing or ablation in human and mouse cells impaired mitochondrial DNA replication. On the basis of the synergy observed with replicative DNA polymerases Polγ and Polε, PrimPol is proposed to facilitate replication fork progression by acting as a translesion DNA polymerase or as a specific DNA primase reinitiating downstream of lesions that block synthesis during both mitochondrial and nuclear DNA replication. PrimPol is a second human primase that is able to start DNA chains with dNTPs Identification of PrimPol as a DNA polymerase that tolerates AP sites and 8oxoG lesions PrimPol is located at both DNA compartments, mitochondria, and the nucleus PRIMPOL gene silencing affects mtDNA replication
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