DNA polymerase λ promotes error-free replication through Watson-Crick impairing N1-methyl-deoxyadenosine adduct in conjunction with DNA polymerase ζ.
DNA polymerase λ promotes error-free replication through Watson-Crick impairing N1-methyl-deoxyadenosine adduct in conjunction with DNA polymerase ζ.
复制标题
DOI：
10.1016/j.jbc.2021.100868
复制
发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Prakash L
中科院分区：
文献类型：
--
作者：
Yoon JH;Basu D;Choudhury JR;Prakash S;Prakash L
在之前的研究中，我们发现人类细胞中n1 -甲基脱氧腺苷（1-MeA）加合物的复制是通过三种不同的Polι/Polθ、Polη和polζ依赖途径介导的。基于对Polι/Polθ通路中Polι/Polθ的生化研究，我们推断Polι在插入与1-MeA相反的核苷酸（nt）中起作用，Polθ在从插入的nt延伸合成中起作用；在Polη途径中，我们推断该Pol可以单独通过1-MeA进行复制；然而，在Polζ通路中，插入与1-MeA相反的nt所需的Pol仍未确定。在这项研究中，我们提供了生物化学和遗传证据，证明Polλ在插入与1-MeA相反的正确nt T中起作用，Polζ将从中扩展合成。纯化的Polλ在插入与1-MeA相对的T时的高能力暗示了Polλ的作用-它通常使用W-C碱基配对进行DNA合成-在syn确认中容纳1-MeA并与T形成Hoogsteen碱基对。Polλ通过Hoogsteen碱基配对进行DNA损伤复制的潜力为Polλ在翻译合成中的作用增加了另一个新的方面，除了它作为Polζ的脚手架成分的作用。我们讨论了如何抑制Polλ和Polζ的作用机制，分别插入与1-MeA相反的T并扩展合成。
In a previous study, we showed that replication through the N1-methyl-deoxyadenosine (1-MeA) adduct in human cells is mediated via three different Polι/Polθ, Polη, and Polζ-dependent pathways. Based on biochemical studies with these Pols, in the Polι/Polθ pathway, we inferred a role for Polι in the insertion of a nucleotide (nt) opposite 1-MeA and of Polθ in extension of synthesis from the inserted nt; in the Polη pathway, we inferred that this Pol alone would replicate through 1-MeA; in the Polζ pathway, however, the Pol required for inserting an nt opposite 1-MeA had remained unidentified. In this study, we provide biochemical and genetic evidence for a role for Polλ in inserting the correct nt T opposite 1-MeA, from which Polζ would extend synthesis. The high proficiency of purified Polλ for inserting a T opposite 1-MeA implicates a role for Polλ—which normally uses W-C base pairing for DNA synthesis—in accommodating 1-MeA in a syn confirmation and forming a Hoogsteen base pair with T. The potential of Polλ to replicate through DNA lesions by Hoogsteen base pairing adds another novel aspect to Polλ’s role in translesion synthesis in addition to its role as a scaffolding component of Polζ. We discuss how the action mechanisms of Polλ and Polζ could be restrained to inserting a T opposite 1-MeA and extending synthesis thereafter, respectively.
登录
查看更多内容
影响因子：
16.8
作者：
Ummat, Ajay;Rechkoblit, Olga;Jain, Rinku;Choudhury, Jayati Roy;Johnson, Robert E.;Silverstein, Timothy D.;Buku, Angeliki;Lone, Samer;Prakash, Louise;Prakash, Satya;Aggarwal, Aneel K.
通讯作者：
Aggarwal, Aneel K.
影响因子：
64.8
作者：
Nair, DT;Johnson, RE;Aggarwal, AK
通讯作者：
Aggarwal, AK
DOI：
10.1073/pnas.96.12.6632
发表时间：
1999-06-08
影响因子：
11.1
作者：
Lee, JH;Hwang, GS;Choi, BS
通讯作者：
Choi, BS
影响因子：
5.7
作者：
Nair, DT;Johnson, RE;Aggarwal, AK
通讯作者：
Aggarwal, AK
影响因子：
64.8
作者：
通讯作者：
--