极端嗜热古菌8oxoG DNA糖苷酶的研究进展

Research progress in 8oxoG DNA glycosylases of hyperthermophilic archaea

摘要:

7，8二氢-8-氧鸟嘌呤（7，8-dihydro-8-oxoguanine，8oxoG）是一种常见的DNA损伤碱基。由于8oxoG能够与腺嘌呤配对，在DNA中的8oxoG被修复之前进行复制，DNA将会产生GC→TA的突变，从而造成基因组的不稳定。目前，碱基切除修复（Base excision repair，BER）是修复DNA中8oxoG的经典途径，其中8oxoG DNA糖苷酶（8-oxoguanine DNA glycosylases，OGG）是启动BER途径的关键酶。研究发现，OGG能够识别和切除DNA中的8oxoG，从而阻止细胞内GC→TA突变的积累。目前，OGG分为3个家族：OGG1、OGG2和AGOG （archaeal 8oxoG DNA glycosylase），广泛分布于细菌、古菌和真核生物。古菌基因组的序列表明，它们至少编码一种OGG。目前，对源自细菌和真核生物的OGG已进行了大量的研究，但是关于极端嗜热古菌OGG的研究相对较少，尚处于初期阶段。本文综述了极端嗜热古菌OGG的研究进展，并对今后的研究提出了展望。

Abstract:

7,8-dihydro-8-oxoguanine (7,8-dihydro-8-oxoguanine, 8oxoG) is a common DNA damage base. Because 8oxoG can form a pair with adenine, the replication of 8oxoG before being repaired would lead to the mutation of GC → TA, thereby causing genome instability. Base excision repair (BER) is a typical pathway to repair 8oxoG in DNA, among which 8oxoG DNA glycosylases (OGGs) are the key enzymes that initiate a BER pathway. Previous studies showed that OGG can recognize and excise 8oxoG in DNA, thereby preventing the accumulation of GC → TA mutations in cells. Currently, OGG, which is widely distributed in bacteria, archaea and eukaryotes, has been divided into three families:OGG1, OGG2 and AGOG (archaeal 8oxoG DNA glycosylase). Archaeal genomic sequences suggest that they encode at least one OGG. Currently, a few OGGs of bacteria and eukaryotes have been extensively studied, but there have been several studies on OGGs of hyperthermophilic archaea, which is still in the early stage. Research progress of OGGs of hyperthermophilic archaea was reviewed and the prospects for future research were proposed in this article.