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The absence of the catalytic domains of Saccharomyces cerevisiae DNA polymerase ϵ strongly reduces DNA replication fidelity.酿酒酵母 DNA 聚合酶 ϵ 的催化结构域缺失会严重降低 DNA 复制保真度。
Nucleic Acids Res. 2019 May 7;47(8):3986-3995. doi: 10.1093/nar/gkz048.
3
Structural consequence of the most frequently recurring cancer-associated substitution in DNA polymerase ε.DNA 聚合酶 ε 中最常发生的与癌症相关取代的结构后果。
Nat Commun. 2019 Jan 22;10(1):373. doi: 10.1038/s41467-018-08114-9.
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A recurrent cancer-associated substitution in DNA polymerase ε produces a hyperactive enzyme.一种在 DNA 聚合酶 ε 中反复出现的与癌症相关的取代会产生一种超活性酶。
Nat Commun. 2019 Jan 22;10(1):374. doi: 10.1038/s41467-018-08145-2.
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DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency.DNA 聚合酶 ε 缺陷导致具有可变免疫缺陷的 IMAGe 综合征。
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Germline mutation p.N363K in POLE is associated with an increased risk of colorectal cancer and giant cell glioblastoma.胚系 POLE 突变 p.N363K 与结直肠癌和巨细胞神经胶质瘤风险增加相关。
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POLE gene hotspot mutations in advanced pancreatic cancer.晚期胰腺癌中的 POLE 基因热点突变。
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Polymerase-mediated ultramutagenesis in mice produces diverse cancers with high mutational load.聚合酶介导的超诱变在小鼠中产生具有高突变负荷的多种癌症。
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在芽殖酵母中研究核 DNA 复制酶学的新机遇。

Opportunities for new studies of nuclear DNA replication enzymology in budding yeast.

机构信息

Institute of Molecular Biology (IMB), Ackermannweg 4, 55128, Mainz, Germany.

Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, NIEHS, NIH, DHHS, Research Triangle Park, NC, 27709, USA.

出版信息

Curr Genet. 2020 Apr;66(2):299-302. doi: 10.1007/s00294-019-01023-4. Epub 2019 Sep 6.

DOI:10.1007/s00294-019-01023-4
PMID:31493018
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7058513/
Abstract

Three major eukaryotic DNA polymerases, Polymerases α, δ, and ε (Pols α, δ, and ε), perform the fundamental process of DNA synthesis at the replication fork both accurately and efficiently. In trying to understand the necessity and flexibility of the polymerase usage, we recently reported that budding yeast cells lacking Pol ε exonuclease and polymerase domains (pol2-16) survive, but have severe growth defects, checkpoint activation, increased level of dNTP pools as well as significant increase in the mutation rates. Herein, we suggest new opportunities to distinguish the roles of Pol ε from those of two other eukaryotic B-family DNA polymerases, Pols δ and ζ.

摘要

三种主要的真核生物 DNA 聚合酶,聚合酶α、δ 和 ε(Pols α、δ 和 ε),在复制叉处高效且准确地执行 DNA 合成的基本过程。为了了解聚合酶使用的必要性和灵活性,我们最近报道了缺失 Pol ε 核酸外切酶和聚合酶结构域(pol2-16)的酿酒酵母细胞能够存活,但生长缺陷严重,检查点激活,dNTP 池水平升高,突变率显著增加。在此,我们提出了一种新的方法来区分 Pol ε 与另外两种真核 B 族 DNA 聚合酶 Pols δ 和 ζ 的作用。