碱基切除修复

碱基切除修复（Base excision repair，BER）是细胞修复受损DNA的一种机制，主要用来修补大小较小、对DNA双股螺旋结构影响较小的损伤，包括脱氨、被烷基化或氧化的碱基，如8-羟基鸟嘌呤（英语：8-Oxoguanine）（8-oxoG）、7-甲基鸟苷、黄嘌呤与尿嘧啶等^[1][2]。大小较大、影响DNA结构较大的损伤（如紫外线造成的胸腺嘧啶二聚体）则是由核苷酸切除修复（NER）途径修补^[3]。细菌^[4]、古菌^[5]与真核生物皆有碱基切除修复的机制。

碱基切除修复（BER）示意图

BER的过程首先由DNA糖基酶（英语：DNA glycosylase）移除损伤的碱基，形成AP位点，随后AP核酸内切酶（英语：AP endonuclease）将此位点的磷酸二酯键切除，造成DNA单股断裂，接着再由DNA聚合酶合成缺失的碱基（与一般DNA复制的过程一样有DNA夹参与），可能仅合成单一缺失的碱基后由DNA连接酶完成修补（短补丁修复；short-patch BER），也可能合成2-10个核苷酸以取代下游的若干的核苷酸，由Flap核酸内切酶（英语：Flap endonuclease）将旧有的核苷酸切除后，再由DNA连接酶完成修补（长补丁修复；long-patch BER）^[6]，两途径的选择由DNA损伤种类、细胞周期、细胞分化状态与物种种类等因素决定^[7]。

DNA糖基酶的活性可能随老化而下降，使BER途径的效率降低^[8]。另外BER途径的缺失与数种癌症有关^[9][10]。

参考文献

• 分子与细胞生物学主题

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