Base excision repair of oxidative DNA damage: from mechanism to disease.
Base excision repair of oxidative DNA damage: from mechanism to disease.
复制标题
氧化DNA损伤的基础切除修复：从机制到疾病。
DOI：
10.2741/4555
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发表时间：
2017-03-01
期刊：
影响因子：
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通讯作者：
Freudenthal BD
中科院分区：
文献类型：
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作者：
Whitaker AM;Schaich MA;Smith MR;Flynn TS;Freudenthal BD
活性氧不断攻击DNA的结构，导致核碱基的氧化和断裂。氧化DNA损伤本身及其修复介导了许多普遍的人类疾病的进展。清除氧化性DNA损伤并维持基因组完整性的主要途径是碱基切除修复（BER）。结构常常决定功能的格言已被证明是正确的，因为许多最近的结构生物学研究有助于阐明在受损DNA修复过程中关键BER酶所使用的分子机制。这篇综述的重点是单个BER酶的机制细节和这些酶在人类疾病，包括癌症和神经系统疾病的发生和进展中的关联。扩展这些结构和生化研究，以进一步阐明仍然难以捉摸的BER机制，并将我们的努力集中在获得对这些酶如何形成共复合物以促进DNA修复的更好理解上，这是理解BER如何促进人类疾病以及如何操纵它来改变患者结果的关键下一步。
Reactive oxygen species continuously assault the structure of DNA resulting in oxidation and fragmentation of the nucleobases. Both oxidative DNA damage itself and its repair mediate the progression of many prevalent human maladies. The major pathway tasked with removal of oxidative DNA damage, and hence maintaining genomic integrity, is base excision repair (BER). The aphorism that structure often dictates function has proven true, as numerous recent structural biology studies have aided in clarifying the molecular mechanisms used by key BER enzymes during the repair of damaged DNA. This review focuses on the mechanistic details of the individual BER enzymes and the association of these enzymes during the development and progression of human diseases, including cancer and neurological diseases. Expanding on these structural and biochemical studies to further clarify still elusive BER mechanisms, and focusing our efforts toward gaining an improved appreciation of how these enzymes form co-complexes to facilitate DNA repair is a crucial next step toward understanding how BER contributes to human maladies and how it can be manipulated to alter patient outcomes.