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基因组 DNA 中 5- 甲醛胞嘧啶的形成和生物学后果。

Formation and biological consequences of 5-Formylcytosine in genomic DNA.

机构信息

State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, College of Chemistry, Nankai University, Tianjin, 300071, China.

State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, College of Chemistry, Nankai University, Tianjin, 300071, China.

出版信息

DNA Repair (Amst). 2019 Sep;81:102649. doi: 10.1016/j.dnarep.2019.102649. Epub 2019 Jul 8.

DOI:10.1016/j.dnarep.2019.102649
PMID:31303545
Abstract

5-Formyl-2'-deoxycytidine (5fdC) is a naturally occurring nucleobase that is broadly distributed in genomic DNA. 5fdC is produced via the oxidation of 5-methylcytosine (5mdC) by ten-eleven translocation enzyme (TET) and can be further converted to 5-carboxylcytosine (5cadC) by TET. Both 5fdC and 5cadC can be restored to dC by TDG-mediated base excision repair and direct deformylation/decarboxylation. Thus, 5fdC is considered an intermediate in the TET-mediated DNA demethylation pathway. 5fdC also alters the structure and stability of genomic DNA and affects genetic expression. This review summarizes the recent research on 5fdC, detailing its formation, detection and distribution, biological functions and transformation in cells. The challenges and future prospects to further explore the function and metabolism of 5fdC are briefly discussed at the end.

摘要

5- 甲酰基-2'-脱氧胞苷(5fdC)是一种广泛分布于基因组 DNA 中的天然存在的核碱基。5fdC 是由 TET 氧化 5-甲基胞嘧啶(5mdC)产生的,可进一步由 TET 转化为 5-羧基胞嘧啶(5cadC)。5fdC 和 5cadC 均可通过 TDG 介导的碱基切除修复和直接去甲酰基/脱羧基作用恢复为 dC。因此,5fdC 被认为是 TET 介导的 DNA 去甲基化途径中的中间产物。5fdC 还改变了基因组 DNA 的结构和稳定性,并影响遗传表达。本综述总结了 5fdC 的最新研究进展,详细介绍了其在细胞中的形成、检测和分布、生物学功能和转化。最后简要讨论了进一步探索 5fdC 功能和代谢的挑战和未来前景。

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