Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: Implications for cancer and neuronal damage
Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: Implications for cancer and neuronal damage
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DOI：
10.1073/pnas.94.7.3290
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发表时间：
1997-04-01
影响因子：
11.1
通讯作者：
Ames, BN
中科院分区：
文献类型：
--
作者：
Blount, BC;Mack, MM;Ames, BN
叶酸缺乏导致尿嘧啶大量掺入人DNA(每个细胞400万)和染色体断裂，可能的机制是DUMP甲基化缺陷和随后DNA聚合酶将尿嘧啶掺入DIVA。在DNA中尿嘧啶的修复过程中，会形成短暂的缺口；两个相对的缺口可能会导致染色体断裂，高DNA尿嘧啶水平和升高的微核率(染色体断裂的衡量标准)都可以通过叶酸治疗而逆转。相当大比例的美国人口叶酸水平较低，与尿嘧啶误结合和染色体断裂有关，这种断裂可能会增加人类患癌症的风险和与叶酸缺乏相关的认知缺陷。
Folate deficiency causes massive incorporation of uracil into human DNA (4 million per cell) and chromosome breaks, The likely mechanism is the deficient methylation of dUMP to dTMP and subsequent incorporation of uracil into DIVA by DNA polymerase. During repair of uracil in DNA, transient nicks are formed; two opposing nicks could lead to chromosome breaks, Both high DNA uracil levels and elevated micronucleus frequency (a measure of chromosome breaks) are reversed by folate administration. A significant proportion of the U.S. population has low folate levels, in the range associated with elevated uracil misincorporation and chromosome breaks, Such breaks could contribute to the increased risk of cancer and cognitive defects associated with folate deficiency in humans.