Escherichia coli Fpg glycosylase is nonrendundant and required for the rapid global repair of oxidized purine and pyrimidine damage in vivo.
Escherichia coli Fpg glycosylase is nonrendundant and required for the rapid global repair of oxidized purine and pyrimidine damage in vivo.
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大肠杆菌 Fpg 糖基化酶是非冗余的，是体内氧化嘌呤和嘧啶损伤快速整体修复所必需的。
DOI：
10.1016/j.jmb.2011.05.004
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发表时间：
2011
影响因子：
5.6
通讯作者：
Courcelle,Justin
中科院分区：
文献类型：
--
作者：
Schalow,BrandyJ;Courcelle,CharmainT;Courcelle,Justin
核酸内切酶(Endo)III和甲酰胺基嘧啶-N-糖基酶(FPG)是大肠杆菌中两种主要的DNA糖基化酶，它们能清除氧化碱基损伤。在细胞抽提物和纯化形式中，Endo III通常对氧化的嘧啶更活跃，而FPG对氧化的嘌呤更活跃。然而，这些酶的底物特异性在体外部分重叠。关于这些酶在氧化损伤后恢复基因组模板方面的相对贡献，人们知之甚少。在这项研究中，我们研究了Endo III和FPG在过氧化氢处理后如何有效地修复其体内的氧化底物。我们发现，FPG是非冗余的，需要快速去除其在染色体上的底物损伤。此外，FPG还修复了Endo III识别的很大一部分损伤，表明它在体内对嘌呤损伤和嘧啶损伤的整体修复中发挥着重要作用。相比之下，Endo III不影响FPG底物的修复率，只负责修复体内自身底物损伤的一部分。缺乏Endo VIII或核苷酸切除修复并不显著影响体内FPG或Endo III底物的整体修复。令人惊讶的是，在所有被研究的突变体中，在氧化DNA损伤之后，复制都恢复了，即使DNA中仍然存在损伤，这表明存在一种有效的机制来处理或克服复制过程中遇到的氧化损伤。
Endonuclease (Endo) III and formamidopyrimidine-N-glycosylase (Fpg) are two of the predominant DNA glycosylases inEscherichia colithat remove oxidative base damage. In cell extracts and purified form, Endo III is generally more active toward oxidized pyrimidines, while Fpg is more active towards oxidized purines. However, the substrate specificities of these enzymes partially overlapin vitro. Less is known about the relative contribution of these enzymes in restoring the genomic template following oxidative damage. In this study, we examined how efficiently Endo III and Fpg repair their oxidative substratesin vivofollowing treatment with hydrogen peroxide. We found that Fpg was nonredundant and required to rapidly remove its substrate lesions on the chromosome. In addition, Fpg also repaired a significant portion of the lesions recognized by Endo III, suggesting that it plays a prominent role in the global repair of both purine damage and pyrimidine damagein vivo. By comparison, Endo III did not affect the repair rate of Fpg substrates and was only responsible for repairing a subset of its own substrate lesionsin vivo. The absence of Endo VIII or nucleotide excision repair did not significantly affect the global repair of either Fpg or Endo III substratesin vivo. Surprisingly, replication recovered after oxidative DNA damage in all mutants examined, even when lesions persisted in the DNA, suggesting the presence of an efficient mechanism to process or overcome oxidative damage encountered during replication.
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影响因子：
3.8
作者：
Rezaee M;Alizadeh E;Hunting D;Sanche L
通讯作者：
Sanche L
影响因子：
64.8
作者：
MELLON, I;HANAWALT, PC
通讯作者：
HANAWALT, PC
DOI：
10.1073/pnas.89.8.3375
发表时间：
1992-04-15
影响因子：
11.1
作者：
PARK, EM;SHIGENAGA, MK;AMES, BN
通讯作者：
AMES, BN
大肠杆菌诱变遗传学：跨损伤聚合酶（Pol II、IV 和 V）的各种组合处理损伤/序列背景多样性。
影响因子：
3.8
作者：
J. Wagner;Hélène Etienne;R. Janel;R. Fuchs
通讯作者：
R. Fuchs
影响因子：
4.8
作者：
C. Tamm;H. Shapiro;R. Lipshitz;E. Chargaff
通讯作者：
E. Chargaff