Antimutator variants of DNA polymerases.
Antimutator variants of DNA polymerases.
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DOI：
10.3109/10409238.2011.620941
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发表时间：
2011-12
影响因子：
6.5
通讯作者：
Preston BD
中科院分区：
文献类型：
--
作者：
Herr AJ;Williams LN;Preston BD
进化平衡了DNA复制的速度和准确性，以优化复制适应性和遗传稳定性。除了来自其他来源（如DNA损伤）的背景突变率之外，没有选择压力来提高DNA复制保真度。然而，DNA聚合酶仍然可以接受氨基酸取代，从而降低内在错误率。在这里，我们回顾了DNA聚合酶的这些“抗诱变”变化，并讨论了它们揭示的复制保真度机制。对噬菌体T4 DNA聚合酶（T4 Pol）的开创性研究建立了一个范例，即抗诱变子氨基酸取代通过以牺牲聚合酶的加工能力为代价提高校对效率来减少复制错误。在细菌Pol I和III以及酵母Pol δ的校对缺陷“突变子”衍生物中发现了抗诱变子替换，这表明一定存在其他的抗诱变机制。值得注意的是，Pol I、Pol III和Pol δ中许多受影响的氨基酸位置与最初的T4 Pol取代相似。DNA聚合酶结构中抗突变子取代的位置表明，它们可能增加核苷酸选择性和/或促进引物末端与聚合酶的分离，从而导致错误核苷酸的排出。如果发生错误掺入，从聚合酶结构域增强的引物解离可能通过内在的核酸外切酶或通过交替的细胞校对活动改善顺式的校对。总之，这些研究表明，自然选择可以很容易地将自适应突变表型后的复制错误率恢复到可持续水平。
Evolution balances DNA replication speed and accuracy to optimize replicative fitness and genetic stability. There is no selective pressure to improve DNA replication fidelity beyond the background mutation rate from other sources, such as DNA damage. However, DNA polymerases remain amenable to amino-acid substitutions that lower intrinsic error rates. Here, we review these ‘antimutagenic’ changes in DNA polymerases and discuss what they reveal about mechanisms of replication fidelity. Pioneering studies with bacteriophage T4 DNA polymerase (T4 Pol) established the paradigm that antimutator amino-acid substitutions reduce replication errors by increasing proofreading efficiency at the expense of polymerase processivity. The discoveries of antimutator substitutions in proofreading-deficient ‘mutator’ derivatives of bacterial Pols I and III and yeast Pol δ suggest there must be additional antimutagenic mechanisms. Remarkably, many of the affected amino-acid positions from Pol I, Pol III, and Pol δ are similar to the original T4 Pol substitutions. The locations of antimutator substitutions within DNA polymerase structures suggest that they may increase nucleotide selectivity and/or promote dissociation of primer termini from polymerases poised for misincorporation, leading to expulsion of incorrect nucleotides. If misincorporation occurs, enhanced primer dissociation from polymerase domains may improve proofreading in cis by an intrinsic exonuclease or in trans by alternate cellular proofreading activities. Together, these studies reveal that natural selection can readily restore replication error rates to sustainable levels following an adaptive mutator phenotype.
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影响因子：
64.5
作者：
Bailey, Scott;Wing, Richard A.;Steitz, Thomas A.
通讯作者：
Steitz, Thomas A.
DOI：
10.1101/sqb.2000.65.81
发表时间：
2000-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Bebenek, K;Kunkel, TA
通讯作者：
Kunkel, TA
DOI：
10.1073/pnas.0607057103
发表时间：
2006-11-28
影响因子：
11.1
作者：
Bielas, Jason H.;Loeb, Keith R.;Loeb, Lawrence A.
通讯作者：
Loeb, Lawrence A.
影响因子：
14.9
作者：
Aravind, L;Koonin, EV
通讯作者：
Koonin, EV
DOI：
10.1101/sqb.1968.033.01.039
发表时间：
1968-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
DRAKE, JW;ALLEN, EF
通讯作者：
ALLEN, EF