Targeted deletion of alkylpurine-DNA-N-glycosylase in mice eliminates repair of 1,N-6-ethenoadenine and hypoxanthine but not of 3,N-4-ethenocytosine or 8-oxoguanine
Targeted deletion of alkylpurine-DNA-N-glycosylase in mice eliminates repair of 1,N-6-ethenoadenine and hypoxanthine but not of 3,N-4-ethenocytosine or 8-oxoguanine
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DOI：
10.1073/pnas.94.24.12869
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发表时间：
1997-11-25
影响因子：
11.1
通讯作者：
Elder, RH
中科院分区：
文献类型：
--
作者：
Hang, B;Singer, B;Elder, RH
此前曾报道，在体外，DNA 修复酶会从 DNA 中释放 1,N-6-乙烯腺嘌呤 (epsilon A)、脱氨基腺嘌呤（次黄嘌呤，Hx）和 7,8-二氢-8-氧代鸟嘌呤 (8-oxoG)，但不会释放 3,N-4-乙烯胞嘧啶 (epsilon C) 烷基嘌呤-DNA-N-糖基化酶 (APNG)，为了评估 APNG 对修复体内每种突变损伤的潜在贡献，我们使用了 APNG 缺失突变小鼠和野生型对照组织的无细胞提取物，确定了这些提取物裂解含有单个修饰碱基的特定寡聚体的能力，结果表明， 这些敲除小鼠完全缺乏对含有 epsilon A 和 Hx 的寡核苷酸的活性，但保留了对 epsilon C 和 8-oxoG 的野生型活性水平。 (ii) 两种结构密切相关的诱变加合物 epsilon A 和 epsilon C 由单独的基因产物修复； (iii) APNG 对 8-oxoG 的修复没有可检测到的贡献。
It has previously been reported that 1,N-6-ethenoadenine (epsilon A), deaminated adenine (hypoxanthine, Hx), and 7,8-dihydro-8-oxoguanine (8-oxoG), but not 3,N-4-ethenocytosine (epsilon C), are released from DNA in vitro by the DNA repair enzyme alkylpurine-DNA-N-glycosylase (APNG), To assess the potential contribution of APNG to the repair of each of these mutagenic lesions in vivo, we have used cell-free extracts of tissues from APNG-null mutant mice and wild-type controls, The ability of these extracts to cleave defined oligomers containing a single modified base was determined, The results showed that both testes and liver cells of these knockout mice completely lacked activity toward oligonucleotides containing epsilon A and Hx, but retained wild-type levels of activity for epsilon C and 8-oxoG, These findings indicate that (i) the previously identified epsilon A-DNA glycosylase and Hx-DNA glycosylase activities are functions of APNG; (ii) the two structurally closely related mutagenic adducts epsilon A and epsilon C are repaired by separate gene products; and (iii) APNG does not contribute detectably to the repair of 8-oxoG.