Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-1079, USA.
Cell Mol Life Sci. 2010 Nov;67(21):3573-87. doi: 10.1007/s00018-010-0485-5. Epub 2010 Aug 17.
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.
活性氧物种在体内产生，并作为一种毒性反应被诱导产生，会导致哺乳动物和其他基因组中的几十个氧化或修饰碱基和/或单链断裂。这些损伤主要通过保守的碱基切除修复（BER）途径进行修复。BER 是由 DNA 糖苷酶切除氧化或修饰碱基起始的，导致损伤部位形成无碱基（AP）位点或链断裂。通过实验和建模方法的结构分析表明，哺乳动物 DNA 糖苷酶中通常存在一个无规卷曲片段，位于 N 或 C 末端，这是其细菌原型所没有的特征标志。最近对 DNA 代谢蛋白中无规卷曲区域的研究表明，它们在与其他蛋白质和靶 DNA 识别的相互作用中起着重要作用。在这篇综述中，我们讨论了人 DNA 糖苷酶和参与糖苷酶产物加工的 AP 内切酶中无规卷曲片段的独特存在，以及它们在调节修复功能中的关键作用。这些无规卷曲片段还包括翻译后修饰和核定位信号的位点。还讨论了它们结构灵活性的目的论基础。
