5-METHYLCYTOSINE AS AN ENDOGENOUS MUTAGEN IN THE HUMAN LDL RECEPTOR AND P53 GENES
5-METHYLCYTOSINE AS AN ENDOGENOUS MUTAGEN IN THE HUMAN LDL RECEPTOR AND P53 GENES
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DOI：
10.1126/science.1697983
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发表时间：
1990-09-14
期刊：
影响因子：
56.9
通讯作者：
JONES, PA
中科院分区：
文献类型：
--
作者：
RIDEOUT, WM;COETZEE, GA;JONES, PA
直接基因组测序显示，胞嘧啶残基已知已经历了生殖细胞突变的低密度脂蛋白受体基因或体细胞突变的p53肿瘤抑制基因甲基化在所有正常的人体组织分析。因此，这些突变应评分为从5-甲基胞嘧啶到胸腺嘧啶的转换，而不是从胞嘧啶到胸腺嘧啶的转换。甲基化胞嘧啶只发生在CpG二核苷酸上，尽管在人类DNA中明显不足，但它是所有已知疾病相关点突变的30%以上的位点。因此，5-甲基胞嘧啶在人体中作为内源性诱变剂和致癌物发挥作用，因为甲基化似乎使胞嘧啶残基突变的可能性增加至少10倍。
Direct genomic sequencing revealed that cytosine residues known to have undergone a germ-line mutation in the low density lipoprotein receptor gene or somatic mutations in the p53 tumor suppressor gene were methylated in all normal human tissues analyzed. Thus, these mutations should be scored as transitions from 5-methylcytosine to thymine rather than from cytosine to thymine. Methylated cytosines occur exclusively at CpG dinucleotides, which, although markedly underrepresented in human DNA, are sites for more than 30 percent of all known disease-related point mutations. Thus, 5-methylcytosine functions as an endogenous mutagen and carcinogen in humans, in that methylation seems to increase the potential for mutation at cytosine residues at least by a factor of 10.