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PrimPol 对于 mtDNA 损伤后的复制起始是必需的。

PrimPol is required for replication reinitiation after mtDNA damage.

机构信息

Department of Environmental and Biological Sciences, University of Eastern Finland, 80101 Joensuu, Finland.

Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.

出版信息

Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11398-11403. doi: 10.1073/pnas.1705367114. Epub 2017 Oct 9.

DOI:10.1073/pnas.1705367114
PMID:29073063
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5664498/
Abstract

Eukaryotic PrimPol is a recently discovered DNA-dependent DNA primase and translesion synthesis DNA polymerase found in the nucleus and mitochondria. Although PrimPol has been shown to be required for repriming of stalled replication forks in the nucleus, its role in mitochondria has remained unresolved. Here we demonstrate in vivo and in vitro that PrimPol can reinitiate stalled mtDNA replication and can prime mtDNA replication from nonconventional origins. Our results not only help in the understanding of how mitochondria cope with replicative stress but can also explain some controversial features of the lagging-strand replication.

摘要

真核生物 PrimPol 是一种新发现的依赖于 DNA 的 DNA 引发酶和跨损伤合成 DNA 聚合酶,存在于细胞核和线粒体中。虽然已经证明 PrimPol 对于核内停滞复制叉的重新引发是必需的,但它在线粒体中的作用仍未解决。在这里,我们体内和体外证明 PrimPol 可以重新启动停滞的 mtDNA 复制,并可以从非常规起点引发 mtDNA 复制。我们的结果不仅有助于理解线粒体如何应对复制应激,还可以解释滞后链复制的一些有争议的特征。

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本文引用的文献

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The role of mitochondria in cardiac development and protection.线粒体在心脏发育和保护中的作用。
Free Radic Biol Med. 2017 May;106:345-354. doi: 10.1016/j.freeradbiomed.2017.02.032. Epub 2017 Feb 17.
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Single-Molecule Analysis of mtDNA Replication Uncovers the Basis of the Common Deletion.单分子分析 mtDNA 复制揭示了常见缺失的基础。
Mol Cell. 2017 Feb 2;65(3):527-538.e6. doi: 10.1016/j.molcel.2016.12.014. Epub 2017 Jan 19.
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Replication fork instability and the consequences of fork collisions from rereplication.复制叉不稳定性及再复制导致的复制叉碰撞后果。
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Oxidative DNA damage stalls the human mitochondrial replisome.氧化 DNA 损伤使人类线粒体复制体停滞。
Sci Rep. 2016 Jul 1;6:28942. doi: 10.1038/srep28942.
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High-resolution genomic assays provide insight into the division of labor between TLS and HDR in mammalian replication of damaged DNA.高分辨率基因组分析为深入了解哺乳动物受损DNA复制过程中跨损伤合成(TLS)与同源重组修复(HDR)之间的分工提供了线索。
DNA Repair (Amst). 2016 Aug;44:59-67. doi: 10.1016/j.dnarep.2016.05.007. Epub 2016 May 16.
6
Repriming by PrimPol is critical for DNA replication restart downstream of lesions and chain-terminating nucleosides.PrimPol介导的重新引发对于损伤和链终止核苷下游的DNA复制重启至关重要。
Cell Cycle. 2016 Aug 2;15(15):1997-2008. doi: 10.1080/15384101.2016.1191711. Epub 2016 May 26.
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Single-strand gap repair involves both RecF and RecBCD pathways.单链缺口修复涉及RecF和RecBCD两条途径。
Curr Genet. 2016 Aug;62(3):519-21. doi: 10.1007/s00294-016-0575-5. Epub 2016 Feb 13.
8
PrimPol-deficient cells exhibit a pronounced G2 checkpoint response following UV damage.PrimPol 缺陷细胞在紫外线损伤后表现出明显的 G2 期检查点反应。
Cell Cycle. 2016;15(7):908-18. doi: 10.1080/15384101.2015.1128597. Epub 2015 Dec 22.
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PrimPol Is Required for Replicative Tolerance of G Quadruplexes in Vertebrate Cells.脊椎动物细胞中G-四链体的复制耐受性需要PrimPol。
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Low doses of ultraviolet radiation and oxidative damage induce dramatic accumulation of mitochondrial DNA replication intermediates, fork regression, and replication initiation shift.低剂量紫外线辐射和氧化损伤会导致线粒体DNA复制中间体大量积累、叉形结构倒退以及复制起始位点转移。
Mol Biol Cell. 2015 Nov 15;26(23):4197-208. doi: 10.1091/mbc.E15-06-0390. Epub 2015 Sep 23.