The current state of eukaryotic DNA base damage and repair.
The current state of eukaryotic DNA base damage and repair.
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DOI：
10.1093/nar/gkv1136
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发表时间：
2015-12-02
影响因子：
14.9
通讯作者：
Doetsch PW
中科院分区：
文献类型：
--
作者：
Bauer NC;Corbett AH;Doetsch PW
DNA损伤是生命的自然灾害。最常见的DNA损伤是由氧化、烷基化、脱氨和自发水解引起的碱基、糖和单链断裂损伤。如果不进行修复，这些损伤可能会在基因组中固定为永久性突变。因此，进化导致了一些高度保守的、部分冗余的途径来修复或减轻DNA碱基损伤的影响。这些途径的生化机制已经得到了很好的表征，这项工作的影响最近被托马斯·林达尔、阿齐兹·桑卡尔和保罗·莫德里奇选为2015年诺贝尔化学奖的获得者，以表彰他们在定义DNA修复途径方面的开创性工作。然而，这些修复途径是如何调控和相互联系的仍有待阐明。本文综述了真核生物中经典的碱基切除修复和链切割途径，包括酿酒酵母和人类，以及DNA碱基损伤修复领域面临的一些重要问题和挑战。
DNA damage is a natural hazard of life. The most common DNA lesions are base, sugar, and single-strand break damage resulting from oxidation, alkylation, deamination, and spontaneous hydrolysis. If left unrepaired, such lesions can become fixed in the genome as permanent mutations. Thus, evolution has led to the creation of several highly conserved, partially redundant pathways to repair or mitigate the effects of DNA base damage. The biochemical mechanisms of these pathways have been well characterized and the impact of this work was recently highlighted by the selection of Tomas Lindahl, Aziz Sancar and Paul Modrich as the recipients of the 2015 Nobel Prize in Chemistry for their seminal work in defining DNA repair pathways. However, how these repair pathways are regulated and interconnected is still being elucidated. This review focuses on the classical base excision repair and strand incision pathways in eukaryotes, considering both Saccharomyces cerevisiae and humans, and extends to some important questions and challenges facing the field of DNA base damage repair.