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线粒体DNA复制:从PrimPol角度看

Mitochondrial DNA replication: a PrimPol perspective.

作者信息

Bailey Laura J, Doherty Aidan J

机构信息

Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, U.K.

出版信息

Biochem Soc Trans. 2017 Apr 15;45(2):513-529. doi: 10.1042/BST20160162.

DOI:10.1042/BST20160162
PMID:28408491
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5390496/
Abstract

PrimPol, ase-ymerase), the most recently identified eukaryotic polymerase, has roles in both nuclear and mitochondrial DNA maintenance. PrimPol is capable of acting as a DNA polymerase, with the ability to extend primers and also bypass a variety of oxidative and photolesions. In addition, PrimPol also functions as a primase, catalysing the preferential formation of DNA primers in a zinc finger-dependent manner. Although PrimPol's catalytic activities have been uncovered , we still know little about how and why it is targeted to the mitochondrion and what its key roles are in the maintenance of this multicopy DNA molecule. Unlike nuclear DNA, the mammalian mitochondrial genome is circular and the organelle has many unique proteins essential for its maintenance, presenting a differing environment within which PrimPol must function. Here, we discuss what is currently known about the mechanisms of DNA replication in the mitochondrion, the proteins that carry out these processes and how PrimPol is likely to be involved in assisting this vital cellular process.

摘要

PrimPol(一种无引物酶活性的聚合酶)是最近发现的真核生物聚合酶,在核DNA和线粒体DNA维持中均发挥作用。PrimPol能够作为DNA聚合酶发挥作用,具有延伸引物的能力,还能绕过多种氧化损伤和光损伤。此外,PrimPol还作为一种引发酶发挥作用,以锌指依赖的方式催化DNA引物的优先形成。尽管PrimPol的催化活性已被揭示,但我们对其如何以及为何定位于线粒体,以及它在维持这种多拷贝DNA分子中的关键作用仍知之甚少。与核DNA不同,哺乳动物线粒体基因组是环状的,该细胞器有许多维持其功能所必需的独特蛋白质,这为PrimPol发挥作用提供了一个不同的环境。在这里,我们讨论目前已知的线粒体DNA复制机制、执行这些过程的蛋白质,以及PrimPol可能如何参与协助这一重要的细胞过程。

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Mitochondrial DNA replication: a PrimPol perspective.线粒体DNA复制:从PrimPol角度看
Biochem Soc Trans. 2017 Apr 15;45(2):513-529. doi: 10.1042/BST20160162.
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本文引用的文献

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PrimPol-Prime Time to Reprime.PrimPol——重新启动的黄金时机。
Genes (Basel). 2017 Jan 6;8(1):20. doi: 10.3390/genes8010020.
2
Human Mitochondrial Transcription Factor B2 Is Required for Promoter Melting during Initiation of Transcription.人类线粒体转录因子B2是转录起始过程中启动子解链所必需的。
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Significant impact of divalent metal ions on the fidelity, sugar selectivity, and drug incorporation efficiency of human PrimPol.二价金属离子对人类PrimPol的保真度、糖选择性和药物掺入效率有显著影响。
人类线粒体 DNA 复制和缺失形成的机制和病理学。
Biochem J. 2024 Jun 5;481(11):683-715. doi: 10.1042/BCJ20230262.
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Induced pluripotent stem cells derived from patients carrying mitochondrial mutations exhibit altered bioenergetics and aberrant differentiation potential.由携带线粒体突变的患者衍生的诱导多能干细胞表现出改变的生物能量学和异常的分化潜能。
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Mitochondrial Replication Assay (MIRA) for Efficient in situ Quantification of Nascent mtDNA and Protein Interactions with Nascent mtDNA (mitoSIRF).用于高效原位定量新生线粒体DNA及蛋白质与新生线粒体DNA相互作用的线粒体复制分析(MIRA)(线粒体原位RNA免疫沉淀法)
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Deletion of the primase-polymerases encoding gene, located in a mobile element in HB27, leads to loss of function mutation of genes.位于HB27中一个可移动元件内的引发酶-聚合酶编码基因的缺失,导致基因功能丧失突变。
Front Microbiol. 2022 Dec 1;13:1005862. doi: 10.3389/fmicb.2022.1005862. eCollection 2022.
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PrimPol: A Breakthrough among DNA Replication Enzymes and a Potential New Target for Cancer Therapy.PrimPol:DNA 复制酶领域的突破及癌症治疗的新靶点
Biomolecules. 2022 Feb 3;12(2):248. doi: 10.3390/biom12020248.
8
PLK1 regulates the PrimPol damage tolerance pathway during the cell cycle.PLK1在细胞周期中调节PrimPol损伤耐受途径。
Sci Adv. 2021 Dec 3;7(49):eabh1004. doi: 10.1126/sciadv.abh1004.
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Leigh Syndrome: A Tale of Two Genomes.Leigh综合征:两个基因组的故事
Front Physiol. 2021 Aug 11;12:693734. doi: 10.3389/fphys.2021.693734. eCollection 2021.
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Ideas and methods of nonlinear mathematics and theoretical physics in DNA science: the McLaughlin-Scott equation and its application to study the DNA open state dynamics.DNA科学中非线性数学与理论物理的思想和方法:麦克劳克林 - 斯科特方程及其在研究DNA开放状态动力学中的应用
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Human mitochondrial transcription factors TFAM and TFB2M work synergistically in promoter melting during transcription initiation.人类线粒体转录因子TFAM和TFB2M在转录起始过程中的启动子解链中协同发挥作用。
Nucleic Acids Res. 2017 Jan 25;45(2):861-874. doi: 10.1093/nar/gkw1157. Epub 2016 Nov 29.
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Structure and mechanism of human PrimPol, a DNA polymerase with primase activity.人源 PrimPol 的结构与机制:一种具有引物酶活性的 DNA 聚合酶。
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DNA Polymerase θ: A Unique Multifunctional End-Joining Machine.DNA聚合酶θ:一种独特的多功能末端连接机器。
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New Insights into the Mechanism of DNA Duplication by the Eukaryotic Replisome.真核复制体复制 DNA 的机制的新见解。
Trends Biochem Sci. 2016 Oct;41(10):859-871. doi: 10.1016/j.tibs.2016.07.011. Epub 2016 Aug 20.
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POLRMT regulates the switch between replication primer formation and gene expression of mammalian mtDNA.POLRMT 调控哺乳动物 mtDNA 复制引物形成与基因表达之间的转换。
Sci Adv. 2016 Aug 5;2(8):e1600963. doi: 10.1126/sciadv.1600963. eCollection 2016 Aug.
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Length heterogeneity at conserved sequence block 2 in human mitochondrial DNA acts as a rheostat for RNA polymerase POLRMT activity.人类线粒体DNA中保守序列块2的长度异质性充当RNA聚合酶POLRMT活性的变阻器。
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Pathological ribonuclease H1 causes R-loop depletion and aberrant DNA segregation in mitochondria.病理性核糖核酸酶H1导致线粒体中R环耗竭和异常DNA分离。
Proc Natl Acad Sci U S A. 2016 Jul 26;113(30):E4276-85. doi: 10.1073/pnas.1600537113. Epub 2016 Jul 8.