Molecular snapshots of APE1 proofreading mismatches and removing DNA damage.
Molecular snapshots of APE1 proofreading mismatches and removing DNA damage.
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APE1校对不匹配和去除DNA损伤的分子快照。
DOI：
10.1038/s41467-017-02175-y
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发表时间：
2018-01-26
影响因子：
16.6
通讯作者：
Freudenthal BD
中科院分区：
文献类型：
--
作者：
Whitaker AM;Flynn TS;Freudenthal BD
人无嘌呤/无嘧啶(AP)核酸内切酶1(APE1)是一种重要的DNA修复酶，它通过两种不同的活性来处理DNA损伤：(1)AP-内切酶和(2)3‘至5’外切酶。AP-内切酶活性在AP-位点裂解，而核酸外切酶活性消除较大的3‘错配和DNA损伤，产生适合下游修复的干净DNA末端。核酸外切酶反应的分子细节，以及一个活性部位如何容纳各种有毒的DNA修复中间体，尽管具有重要的生物学意义，但仍然难以捉摸。在这里，我们报告了多张高分辨率的APE1-DNA结构快照，揭示了APE1如何通过非碱基翻转机制将3‘端错配和DNA损伤放置在螺旋内DNA空腔内。DNA缺口、错配/受损碱基的不稳定和DNA的弯曲促进了这一过程。这些结果说明了APE1如何清洁DNA脏端，为下游修复酶产生合适的底物。脱氧核糖核酸内切酶1(APE1)是一种重要的DNA修复酶，具有核酸内切酶和核酸外切酶的活性。在这里，作者提出了DNA结合的人APE1晶体结构，使人们对其核酸外切酶机制有了深入的了解。
Human apurinic/apyrimidinic (AP) endonuclease 1 (APE1) is an essential DNA repair enzyme which uses a single active site to process DNA damage via two distinct activities: (1) AP-endonuclease and (2) 3′ to 5′ exonuclease. The AP-endonuclease activity cleaves at AP-sites, while the exonuclease activity excises bulkier 3′ mismatches and DNA damage to generate clean DNA ends suitable for downstream repair. Molecular details of the exonuclease reaction and how one active site can accommodate various toxic DNA repair intermediates remains elusive despite being biologically important. Here, we report multiple high-resolution APE1–DNA structural snapshots revealing how APE1 removes 3′ mismatches and DNA damage by placing the 3′ group within the intra-helical DNA cavity via a non-base flipping mechanism. This process is facilitated by a DNA nick, instability of a mismatched/damaged base, and bending of the DNA. These results illustrate how APE1 cleanses DNA dirty-ends to generate suitable substrates for downstream repair enzymes. The essential DNA repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1) has both endonuclease and exonuclease activities. Here, the authors present DNA bound human APE1 crystal structures which give insights into its exonuclease mechanism.
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影响因子：
16.8
作者：
Freudenthal BD;Beard WA;Cuneo MJ;Dyrkheeva NS;Wilson SH
通讯作者：
Wilson SH
发现聚合酶诱导的氧化核苷酸的细胞毒性。
影响因子：
64.8
作者：
Freudenthal, Bret D.;Beard, William A.;Perera, Lalith;Shock, David D.;Kim, Taejin;Schlick, Tamar;Wilson, Samuel H.
通讯作者：
Wilson, Samuel H.
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：
4.8
作者：
Chou, KM;Kukhanova, M;Cheng, YC
通讯作者：
Cheng, YC
影响因子：
14.9
作者：
ABOULELA, F;KOH, D;MARTIN, FH
通讯作者：
MARTIN, FH