Functions of disordered regions in mammalian early base excision repair proteins.
Functions of disordered regions in mammalian early base excision repair proteins.
复制标题
DOI：
10.1007/s00018-010-0485-5
复制
发表时间：
2010-11
影响因子：
8
通讯作者：
Mitra, Sankar
中科院分区：
文献类型：
--
作者：
Hegde, Muralidhar L.;Hazra, Tapas K.;Mitra, Sankar
关键词：
内源性产生并作为毒性反应诱导的活性氧物质在哺乳动物和其他基因组中产生数十个氧化或修饰的碱基和/或单链断裂。这些病变主要通过保守的碱基切除修复（BER）途径修复。BER起始于DNA糖基化酶切除氧化或修饰的碱基，导致在损伤位点形成脱碱基（AP）位点或链断裂。通过实验和建模方法进行的结构分析表明，存在通常位于N-或C-末端的无序片段，作为哺乳动物DNA糖基化酶的特征性签名，其在细菌原型中不存在。近年来对DNA代谢蛋白非结构区的研究表明，它们在与其他蛋白相互作用和靶DNA识别中起着重要作用。在这篇综述中，我们讨论了人类DNA糖基化酶中独特的无序片段，以及参与糖基化酶产物加工的AP核酸内切酶，以及它们在调节修复功能中的关键作用。这些无序片段还包括翻译后修饰和核定位信号的位点。其结构灵活性的目的论基础进行了讨论。
Reactive oxygen species, generated endogenously and induced as a toxic response, produce several dozen oxidized or modified bases and/or single-strand breaks in mammalian and other genomes. These lesions are predominantly repaired via the conserved base excision repair (BER) pathway. BER is initiated with excision of oxidized or modified bases by DNA glycosylases leading to formation of abasic (AP) site or strand break at the lesion site. Structural analysis by experimental and modeling approaches shows the presence of a disordered segment commonly localized at the N- or C-terminus as a characteristic signature of mammalian DNA glycosylases which is absent in their bacterial prototypes. Recent studies on unstructured regions in DNA metabolizing proteins have indicated their essential role in interaction with other proteins and target DNA recognition. In this review, we have discussed the unique presence of disordered segments in human DNA glycosylases, and AP endonuclease involved in the processing of glycosylase products, and their critical role in regulating repair functions. These disordered segments also include sites for posttranslational modifications and nuclear localization signal. The teleological basis for their structural flexibility is discussed.
登录
查看更多内容
DOI：
10.1073/pnas.82.9.2688
发表时间：
1985-01-01
影响因子：
11.1
作者：
DEMPLE, B;SEDGWICK, B;LINDAHL, T
通讯作者：
LINDAHL, T
影响因子：
2.9
作者：
Dunker, AK;Lawson, JD;Obradovic, Z
通讯作者：
Obradovic, Z
影响因子：
4.8
作者：
Dou, H;Mitra, S;Hazra, TK
通讯作者：
Hazra, TK
影响因子：
5.8
作者：
Dosztányi, Z;Csizmok, V;Simon, I
通讯作者：
Simon, I
影响因子：
4.8
作者：
Das, Aditi;Boldogh, Istvan;Bohr, Vilhelm A.
通讯作者：
Bohr, Vilhelm A.