DNA polymerase θ accomplishes translesion synthesis opposite 1,N6-ethenodeoxyadenosine with a remarkably high fidelity in human cells.
DNA polymerase θ accomplishes translesion synthesis opposite 1,N6-ethenodeoxyadenosine with a remarkably high fidelity in human cells.
复制标题
DNA 聚合酶 δ 在人体细胞中以非常高的保真度完成与 1,N6-乙烯脱氧腺苷相反的跨损伤合成。
DOI：
10.1101/gad.320531.118
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发表时间：
2019
影响因子：
10.5
通讯作者：
Prakash,Satya
中科院分区：
文献类型：
--
作者：
Yoon,Jung-Hoon;Johnson,RobertE;Prakash,Louise;Prakash,Satya
在这里，我们表明，跨损伤合成（TLS）相反的1，N 6-乙烯脱氧腺苷（εdA），破坏沃森-克里克碱基配对，发生通过Pol I/Pol β-，Rev 1-和Polθ-依赖性途径。Pol i/Pol dA的要求与Pol i通过Hoogsteen碱基配对掺入核苷酸对侧εdA的能力和Pol dA延长合成的能力一致。Rev 1聚合酶和Polθ通过交替易错途径传导TLS相反的εdA。引人注目的是，与纯化的Polθ的εdA相反的极容易出错的TLS相反，它在人类细胞中主要执行无错误的TLS。重新配置与εdA相对的活性位点将为Polθ提供在人类细胞中无错误TLS的能力。
Here we show that translesion synthesis (TLS) opposite 1, N 6-ethenodeoxyadenosine (εdA), which disrupts Watson–Crick base pairing, occurs via Polι/Polζ-, Rev1-, and Polθ-dependent pathways. The requirement of Polι/Polζ is consistent with the ability of Polι to incorporate nucleotide opposite εdA by Hoogsteen base pairing and of Polζ to extend synthesis. Rev1 polymerase and Polθ conduct TLS opposite εdA via alternative error-prone pathways. Strikingly, in contrast to extremely error-prone TLS opposite εdA by purified Polθ, it performs predominantly error-free TLS in human cells. Reconfiguration of the active site opposite εdA would provide Polθ the proficiency for error-free TLS in human cells.