Replication-associated repair of adenine:8-oxoguanine mispairs by MYH
Replication-associated repair of adenine:8-oxoguanine mispairs by MYH
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DOI：
10.1016/s0960-9822(02)00686-3
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发表时间：
2002-02-19
期刊：
影响因子：
9.2
通讯作者：
Matsumoto, Y
中科院分区：
文献类型：
--
作者：
Hayashi, H;Tominaga, Y;Matsumoto, Y
细胞 DNA 不断面临氧化的风险。 8-氧鸟嘌呤（8-oxoG）是氧化产生的主要DNA损伤之一，主要通过碱基切除修复来纠正。如果在复制前未对其进行修复，复制性 DNA 聚合酶会在模板链上的 8-oxoG 对面错误插入腺嘌呤 (A)，从而产生 A:8-oxoG 错配 [1]。 MYH 是大肠杆菌 MutY 的哺乳动物同源物，是一种 DNA 糖基化酶，负责通过切除 8-oxoG 对面的腺嘌呤来启动碱基切除修复此类错配 [2]。在这里，使用体内修复系统，我们表明 DNA 复制增强了 A:8-oxoG 错配的修复。MYH 缺陷的小鼠细胞的修复效率低于 MYH 熟练的细胞。用野生型 MYH 表达载体转染 MYH 缺陷细胞提高了 A:8-oxoG 修复的效率，表明这种复制相关修复的很大一部分依赖于 MYH。 PCNA 结合基序被破坏的突变体 MYH 的表达不会增加修复效率，因此表明 PCNA 和 MYH 之间的相互作用对于 MYH 启动的 A:8-oxoG 修复至关重要。
Cellular DNA is constantly exposed to the risk of oxidation. 8-oxoguanine (8-oxoG) is one of the major DNA lesions generated by oxidation, which is primarily corrected by base excision repair. When it is not repaired prior to replication, replicative DNA polymerases yield misinsertion of an adenine (A) opposite the 8-oxoG on the template strand, generating an A:8-oxoG mispair [1]. MYH, a mammalian homolog of Escherichia coli MutY, is a DNA glycosylase responsible for initiating base excision repair of such a mispair by excising the adenine opposite 8-oxoG [2]. Here, using an in vivo repair system, we show that DNA replication enhances the repair of the A:8-oxoG mispair, Repair efficiency was lower in MYH-deficient murine cells than in MYH-proficient cells. Transfection of the MYH-deficient cells with a wild-type MYH expression vector increased the efficiency of A:8-oxoG repair, indicating that a significant part of this replication-associated repair depends on MYH. Expression of a mutant MYH in which the PCNA binding motif was disrupted did not increase the repair efficiency, thus suggesting that the interaction between PCNA and MYH is critical for MYH-initiated repair of A:8-oxoG.