期刊
ACS CHEMICAL BIOLOGY
卷 7, 期 1, 页码 20-30出版社
AMER CHEMICAL SOC
DOI: 10.1021/cb2002895
关键词
Genomic potential; Cytosine deamination; Cytosine methylation; Cytosine oxidation; Active DNA demethylation
资金
- Rita Allen Foundation
- W. W. Smith Charitable Trust
- NIH/NIAID [K08-AI089242]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [K08AI089242] Funding Source: NIH RePORTER
A multitude of functions have evolved around cytosine within DNA, endowing the base with physiological significance beyond simple information storage: This versatility arises from enzymes that chemically modify cytosine to expand the potential of the genome. Some, modifications alter coding sequences, such as deamination of cytosine by AID/APOBEC enzymes to generate immunologic or virologic diversity. Other modifications are critical to epigenetic control, altering gene expression or cellular identity. Of these, cytosine methylation is well understood, in contrast to recently discovered modifications, such as oxidation by TET enzymes to 5-hydroxymethylcytosine. Further complexity results from cytosine demethylation, an enigmatic process that impacts cellular pluripotency. Recent insights help us to propose an integrated DNA demethylation model, accounting for contributions from cytosine oxidation, deamination, and base excision repair. Taken together, this rich medley of alterations renders cytosine a genomic wild card, whose context dependent functions make the base far more than a static letter in the code of life.
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