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.
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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