DNA 聚合酶为跨损伤合成提供了一套策略，以克服氧化生成的损伤。
DNA polymerases provide a canon of strategies for translesion synthesis past oxidatively generated lesions.
机构信息
Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
出版信息
Curr Opin Struct Biol. 2011 Jun;21(3):358-69. doi: 10.1016/j.sbi.2011.03.008. Epub 2011 Apr 7.
Abstract
Deducing the structure of the DNA double helix in 1953 implied the mode of its replication: Watson-Crick (WC) base pairing might instruct an enzyme, now known as the DNA polymerase, during the synthesis of a daughter stand complementary to a single strand of the parental double helix. What has become increasingly clear in the last 60 years, however, is that adducted and oxidatively generated DNA bases are ubiquitous in physiological DNA, and all organisms conserve multiple DNA polymerases specialized for DNA synthesis opposite these damaged templates. Here, we review recent crystal structures depicting replicative and bypass DNA polymerases encountering two typical lesions arising from the oxidation of DNA: abasic sites, which block the replication fork, and the miscoding premutagenic lesion 7,8-dihydro-8-oxoguanine (8-oxoG).
摘要
1953 年，推断 DNA 双螺旋结构意味着其复制模式：沃森-克里克（WC）碱基配对可能指导一种酶，现在称为 DNA 聚合酶，在合成与亲本 DNA 双螺旋中一条单链互补的子链时发挥作用。然而，在过去的 60 年中，越来越明显的是，加合物和氧化生成的 DNA 碱基在生理 DNA 中普遍存在，所有生物体都保留了多种专门用于在这些受损模板上合成 DNA 的 DNA 聚合酶。在这里，我们回顾了最近描述复制和旁路 DNA 聚合酶遇到两种典型 DNA 氧化损伤的晶体结构：碱基缺失，其阻断复制叉；以及易错的前诱变损伤 7,8-二氢-8-氧鸟嘌呤（8-氧鸟嘌呤）。
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本文引用的文献
1
Unique active site promotes error-free replication opposite an 8-oxo-guanine lesion by human DNA polymerase iota.
Proc Natl Acad Sci U S A. 2011 Feb 22;108(8):3210-5. doi: 10.1073/pnas.1013909108. Epub 2011 Feb 7.
2
DNA synthesis across an abasic lesion by yeast REV1 DNA polymerase.
J Mol Biol. 2011 Feb 11;406(1):18-28. doi: 10.1016/j.jmb.2010.12.016. Epub 2010 Dec 15.
3
Structural basis for error-free replication of oxidatively damaged DNA by yeast DNA polymerase η.
Structure. 2010 Nov 10;18(11):1463-70. doi: 10.1016/j.str.2010.08.019.
4
Metal-ion dependence of the active-site conformation of the translesion DNA polymerase Dpo4 from Sulfolobus solfataricus.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Sep 1;66(Pt 9):1013-8. doi: 10.1107/S1744309110029374. Epub 2010 Aug 21.
5
Structure and mechanism of human DNA polymerase eta.
Nature. 2010 Jun 24;465(7301):1044-8. doi: 10.1038/nature09196.
6
Structural basis for the suppression of skin cancers by DNA polymerase eta.
Nature. 2010 Jun 24;465(7301):1039-43. doi: 10.1038/nature09104.
7
Mutagenic conformation of 8-oxo-7,8-dihydro-2'-dGTP in the confines of a DNA polymerase active site.
Nat Struct Mol Biol. 2010 Jul;17(7):889-90. doi: 10.1038/nsmb.1852. Epub 2010 Jun 6.
8
Substitution of Ala for Tyr567 in RB69 DNA polymerase allows dAMP to be inserted opposite 7,8-dihydro-8-oxoguanine .
Biochemistry. 2010 May 18;49(19):4116-25. doi: 10.1021/bi100102s.
9
Replication through an abasic DNA lesion: structural basis for adenine selectivity.
EMBO J. 2010 May 19;29(10):1738-47. doi: 10.1038/emboj.2010.64. Epub 2010 Apr 16.
10
Kinetics of mismatch formation opposite lesions by the replicative DNA polymerase from bacteriophage RB69.
Biochemistry. 2010 Mar 23;49(11):2317-25. doi: 10.1021/bi901488d.
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