Nontraditional Roles of DNA Polymerase Eta Support Genome Duplication and Stability.
Nontraditional Roles of DNA Polymerase Eta Support Genome Duplication and Stability.
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DOI：
10.3390/genes14010175
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发表时间：
2023-01-09
期刊：
影响因子：
3.5
通讯作者：
Eckert, Kristin A. A.
中科院分区：
文献类型：
--
作者：
Eckert, Kristin A. A.
关键词：
DNA聚合酶eta（Pol η）是一种Y家族聚合酶，是POLH基因的产物。POLH突变的常染色体隐性遗传是着色性干皮病变体（一种癌症易感综合征）的原因。这篇综述总结了越来越多的证据，扩大Pol η细胞功能，除了DNA损伤旁路，是维持基因组稳定性的关键。在体外，Pol η通过难以复制的序列显示有效的DNA合成，催化D环延伸，并利用RNA-DNA杂交模板。人Pol η组成性地存在于复制叉处。为了响应复制应激，Pol η在转录和蛋白质水平上上调，并且翻译后修饰调节其在染色质中的定位。大量研究表明，Pol η是有效的常见脆性位点复制和稳定性所必需的。此外，Pol η可以通过蛋白质-蛋白质相互作用被招募到停滞的复制叉，这表明在复制叉恢复中具有更广泛的作用。在体细胞超突变期间，Pol η被错配修复蛋白募集，并且对于VH基因A：T碱基对诱变是必需的。在重复密集基因组的全球背景下，在复制期间招募Pol η以执行专门功能可以通过用碱基取代中断纯重复阵列来促进基因组稳定性。或者，不使Pol η参与基因组复制是昂贵的，因为Pol η的缺失导致不完全复制和增加的染色体不稳定性。
DNA polymerase eta (Pol η) is a Y-family polymerase and the product of the POLH gene. Autosomal recessive inheritance of POLH mutations is the cause of the xeroderma pigmentosum variant, a cancer predisposition syndrome. This review summarizes mounting evidence for expanded Pol η cellular functions in addition to DNA lesion bypass that are critical for maintaining genome stability. In vitro, Pol η displays efficient DNA synthesis through difficult-to-replicate sequences, catalyzes D-loop extensions, and utilizes RNA–DNA hybrid templates. Human Pol η is constitutively present at the replication fork. In response to replication stress, Pol η is upregulated at the transcriptional and protein levels, and post-translational modifications regulate its localization to chromatin. Numerous studies show that Pol η is required for efficient common fragile site replication and stability. Additionally, Pol η can be recruited to stalled replication forks through protein–protein interactions, suggesting a broader role in replication fork recovery. During somatic hypermutations, Pol η is recruited by mismatch repair proteins and is essential for VH gene A:T basepair mutagenesis. Within the global context of repeat-dense genomes, the recruitment of Pol η to perform specialized functions during replication could promote genome stability by interrupting pure repeat arrays with base substitutions. Alternatively, not engaging Pol η in genome duplication is costly, as the absence of Pol η leads to incomplete replication and increased chromosomal instability.
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DOI：
10.1083/jcb.201008076
发表时间：
2011-01-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Göhler T;Sabbioneda S;Green CM;Lehmann AR
通讯作者：
Lehmann AR
影响因子：
3.7
作者：
Tsao WC;Buj R;Aird KM;Sidorova JM;Eckert KA
通讯作者：
Eckert KA
影响因子：
8.8
作者：
Garcia-Exposito L;Bournique E;Bergoglio V;Bose A;Barroso-Gonzalez J;Zhang S;Roncaioli JL;Lee M;Wallace CT;Watkins SC;Opresko PL;Hoffmann JS;O'Sullivan RJ
通讯作者：
O'Sullivan RJ
影响因子：
14.9
作者：
Hile SE;Wang X;Lee MY;Eckert KA
通讯作者：
Eckert KA
影响因子：
11.2
作者：
Barnes, Ryan P.;Tsao, Wei-Chung;Eckert, Kristin A.
通讯作者：
Eckert, Kristin A.