Structure of the human Rev1-DNA-dNTP ternary complex.
Structure of the human Rev1-DNA-dNTP ternary complex.
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DOI：
10.1016/j.jmb.2009.05.026
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发表时间：
2009-07-24
影响因子：
5.6
通讯作者：
Aggarwal, Aneel K.
中科院分区：
文献类型：
--
作者：
Swan, Michael K.;Johnson, Robert E.;Prakash, Louise;Prakash, Satya;Aggarwal, Aneel K.
Y家族DNA聚合酶已被证明在它们的功能和通过DNA损伤复制的策略方面是显著多样的。酵母Rev 1三元复合物的结构揭示了最激进的复制策略，其中聚合酶本身决定了传入核苷酸的身份以及模板碱基的身份。我们在这里展示了这种非常不寻常的策略的许多关键要素在酵母和人Rev 1之间是保守的，包括从DNA螺旋中驱逐模板G以及将传入的dCTP与替代精氨酸残基配对。我们还表明，人类Rev 1的催化核心是由两个大的插入物，I1和I2，其中I1延伸超过20 μ m远离活性位点，并可能作为蛋白质-蛋白质相互作用的平台，特异性Rev 1在人类细胞中的跨损伤DNA合成（TLS）中的作用，I2作为疏水口袋上的“皮瓣”容纳模板G。我们认为，这些新的结构特征是重要的，为人类Rev 1提供更大的自由度，促进有效的和无错误的TLS通过各种各样的庞大的和潜在的致癌性N-dG DNA加合物在人类细胞。
Y family DNA polymerases have proven to be remarkably diverse in their functions and in strategies for replicating through DNA lesions. The structure of yeast Rev1 ternary complex has revealed the most radical replication strategy, where the polymerase itself dictates the identity of the incoming nucleotide, as well as the identity of the templating base. We show here that many of the key elements of this highly unusual strategy are conserved between yeast and human Rev1, including the eviction of template G from the DNA helix and the pairing of incoming dCTP with a surrogate arginine residue. We also show that the catalytic core of human Rev1 is uniquely augmented by two large inserts, I1 and I2, wherein I1 extends >20Å away from the active site and may serve as a platform for protein-protein interactions specific for Rev1’s role in translesion DNA synthesis (TLS) in human cells, and I2 acts as a “flap” on the hydrophobic pocket accommodating the template G. We suggest that these novel structural features are important for providing human Rev1 greater latitude in promoting efficient and error-free TLS through the diverse array of bulky and potentially carcinogenic N-dG DNA adducts in human cells.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
3.6
作者：
Baynton, K;Bresson-Roy, A;Fuchs, RPP
通讯作者：
Fuchs, RPP
DOI：
10.1073/pnas.97.8.3838
发表时间：
2000-04-11
影响因子：
11.1
作者：
Johnson, RE;Prakash, S;Prakash, L
通讯作者：
Prakash, L
影响因子：
14.9
作者：
Davis IW;Leaver-Fay A;Chen VB;Block JN;Kapral GJ;Wang X;Murray LW;Arendall WB 3rd;Snoeyink J;Richardson JS;Richardson DC
通讯作者：
Richardson DC
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL