A SPECIFIC MISMATCH REPAIR EVENT PROTECTS MAMMALIAN-CELLS FROM LOSS OF 5-METHYLCYTOSINE
A SPECIFIC MISMATCH REPAIR EVENT PROTECTS MAMMALIAN-CELLS FROM LOSS OF 5-METHYLCYTOSINE
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DOI：
10.1016/0092-8674(87)90521-6
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发表时间：
1987-09-11
期刊：
影响因子：
64.5
通讯作者：
JIRICNY, J
中科院分区：
文献类型：
--
作者：
BROWN, TC;JIRICNY, J
5-甲基胞嘧啶自发脱氨基形成胸腺嘧啶，从而在 DNA 中产生 G/T 错配。我们通过将特定的 G/T 错配引入 SV40 基因组并确定猿细胞中错配碱基的命运，研究了哺乳动物细胞中解决这些损伤的方式。错配被掺入连接到 BstXI 和 TaqI 限制位点之间的 SV40 DNA 中的 12 bp 合成双链体中。对转染这种修饰 DNA 后获得的 347 个噬斑的分析表明，343 个病例 (99%) 中的错误得到了纠正，揭示了 314 个修复事件有利于鸟嘌呤 (90%)，29 个修复事件有利于胸腺嘧啶 (8%)。无论 DNA 中错配的方向如何，也无论错配是否位于通常甲基化的 CpG 二核苷酸中，都会出现有利于鸟嘌呤的相关性。这些结果证明了一种特定的错配修复途径，可以恢复因 5-甲基胞嘧啶残基脱氨基而丢失的 G/C 对。
5-Methylcytosine spontaneously deaminates to form thymine, thus generating G/T mispairs in DNA. We investigated the way in which these lesions are addressed in mammalian cells by introducing specific G/T mispairs into the genome of SV40 and determining the fate of the mismatched bases in simian cells. Mispairs were incorporated in 12 bp synthetic duplexes ligated into SV40 DNA between the BstXI and TaqI restriction sites. Analysis of 347 plaques obtained after transfection of this modified DNA indicated that mispais were corrected in 343 cases (99%), revealing 314 repair events in favor of guanine (90%) and 29 in favor of thymine (8%). Correlation in favor of guanine occurred regardless of the orientation of the mispair in DNA and regardless of whether the mispair was in the commonly methylated CpG dinucleotide. These results attest to a specific mismatch repair pathway that restores G/C pairs lost through deamination of 5-methylcytosine residues.