Wallace Susan S
Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, The University of Vermont, 95 Carrigan Drive, Stafford Hall, Burlington, VT 05405-0084, USA.
DNA Repair (Amst). 2014 Jul;19:14-26. doi: 10.1016/j.dnarep.2014.03.030. Epub 2014 Apr 26.
This perspective reviews the many dimensions of base excision repair from a 10,000 foot vantage point and provides one person's view on where the field is headed. Enzyme function is considered under the lens of X-ray diffraction and single molecule studies. Base excision repair in chromatin and telomeres, regulation of expression and the role of posttranslational modifications are also discussed in the context of enzyme activities, cellular localization and interacting partners. The specialized roles that base excision repair play in transcriptional activation by active demethylation and targeted oxidation as well as how base excision repair functions in the immune processes of somatic hypermutation and class switch recombination and its possible involvement in retroviral infection are also discussed. Finally the complexities of oxidative damage and its repair and its link to neurodegenerative disorders, as well as the role of base excision repair as a tumor suppressor are examined in the context of damage, repair and aging. By outlining the many base excision repair-related mysteries that have yet to be unraveled, hopefully this perspective will stimulate further interest in the field.
本文从宏观角度综述了碱基切除修复的多个方面，并就该领域的发展方向提出了个人观点。酶的功能是在X射线衍射和单分子研究的视角下进行考量的。染色质和端粒中的碱基切除修复、表达调控以及翻译后修饰的作用也在酶活性、细胞定位和相互作用伙伴的背景下进行了讨论。还讨论了碱基切除修复通过主动去甲基化和靶向氧化在转录激活中所起的特殊作用，以及碱基切除修复在体细胞超突变和类别转换重组的免疫过程中的功能及其可能参与逆转录病毒感染的情况。最后，在损伤、修复和衰老的背景下，研究了氧化损伤及其修复的复杂性及其与神经退行性疾病的联系，以及碱基切除修复作为肿瘤抑制因子的作用。通过概述许多尚未解开的与碱基切除修复相关的谜团，希望本文能激发该领域更多的兴趣。
