Extrinsic proofreading.
Extrinsic proofreading.
复制标题
DOI：
10.1016/j.dnarep.2022.103369
复制
发表时间：
2022-09
期刊：
影响因子：
3.8
通讯作者：
Kunkel, Thomas A.
中科院分区：
文献类型：
--
作者：
Zhou, Zhi-Xiong;Kunkel, Thomas A.
真核生物核DNA基因组的高保真复制涉及三个过程。正确而非错误的dNTPs几乎总是被三种主要的复制酶，DNA聚合酶α， δ和ε所结合。当偶尔插入不正确的碱基时，后面的pol δ和ε也具有3 ‘到5 ’的核酸外切酶活性，可以去除不匹配以允许正确的DNA合成进行。最后，罕见的错配逃避校对活动，存在于新复制的DNA可以通过DNA错配修复去除。在这篇综述中，我们考虑了支持第二种机制，即校对，可以以两种不同的方式运作的假设的证据。由Pol δ或Pol ε引起的引物末端错配可以“本质”校对。这种机制是通过将聚合酶活性位点上的错误插入的碱基直接转移到距离较近的外切酶活性位点上而发生的。内在校对允许错配切除不干预酶解离。另外，相当多的证据表明，三种复制酶中的任何一种产生的错配也可以通过Pol δ的“外在”校对来纠正。当三种复制酶中的任何一种产生的错配最初被放弃时，就会发生外部校对，从而允许Pol δ的外切酶活性位点在复制继续之前直接结合并去除错配。在这里，我们回顾了外在校对显着提高核DNA复制保真度的证据，然后我们简要地考虑了这一过程对进化和疾病的影响。
The high fidelity of replication of the nuclear DNA genome in eukaryotes involves three processes. Correct rather than incorrect dNTPs are almost always incorporated by the three major replicases, DNA polymerases α, δ and ε. When an incorrect base is occasionally inserted, the latter Pols δ and ε also have a 3’ to 5’ exonuclease activity that can remove the mismatch to allow correct DNA synthesis to proceed. Lastly, rare mismatches that escape proofreading activity and are present in newly replicated DNA can be removed by DNA mismatch repair. In this review, we consider evidence supporting the hypothesis that the second mechanism, proofreading, can operate in two different ways. Primer terminal mismatches made by either Pol δ or Pol ε can be ‘intrinsically’ proofread. This mechanism occurs by direct transfer of a misinserted base made at the polymerase active site to the exonuclease active site that is located a short distance away. Intrinsic proofreading allows mismatch excision without intervening enzyme dissociation. Alternatively, considerable evidence suggests that mismatches made by any of the three replicases can also be proofread by ‘extrinsic’ proofreading by Pol δ. Extrinsic proofreading occurs when a mismatch made by any of the three replicases is initially abandoned, thereby allowing the exonuclease active site of Pol δ to bind directly to and remove the mismatch before replication continues. Here we review the evidence that extrinsic proofreading significantly enhances the fidelity of nuclear DNA replication, and we then briefly consider the implications of this process for evolution and disease.
登录
查看更多内容
常见的与癌症相关的DNA聚合酶ε突变会导致异常强的突变器表型，表明富达缺陷与校对丧失不同。
影响因子：
11.2
作者：
Kane DP;Shcherbakova PV
通讯作者：
Shcherbakova PV
影响因子：
16.6
作者：
Garbacz MA;Lujan SA;Burkholder AB;Cox PB;Wu Q;Zhou ZX;Haber JE;Kunkel TA
通讯作者：
Kunkel TA
影响因子：
14.9
作者：
Fortune JM;Stith CM;Kissling GE;Burgers PM;Kunkel TA
通讯作者：
Kunkel TA
影响因子：
3.5
作者：
Church DN;Briggs SE;Palles C;Domingo E;Kearsey SJ;Grimes JM;Gorman M;Martin L;Howarth KM;Hodgson SV;NSECG Collaborators;Kaur K;Taylor J;Tomlinson IP
通讯作者：
Tomlinson IP
影响因子：
16.6
作者：
Burgers PMJ;Kunkel TA
通讯作者：
Kunkel TA