The curious chemical biology of cytosine: deamination, methylation, and oxidation as modulators of genomic potential.
The curious chemical biology of cytosine: deamination, methylation, and oxidation as modulators of genomic potential.
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DOI:
10.1021/cb2002895
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发表时间:
2012-01-20
影响因子:
4
通讯作者:
Kohli, Rahul M.
中科院分区:
文献类型:
--
作者:
Nabel, Christopher S.;Manning, Sara A.;Kohli, Rahul M.
关键词:
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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发表时间:
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