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.
Kohli, Rahul M.
中科院分区:
生物学2区
文献类型:
--
作者:
Nabel, Christopher S.;Manning, Sara A.;Kohli, Rahul M.

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DNA中的胞嘧啶周围已经进化出了许多功能,赋予了碱基超越简单信息存储的生理意义。这种多功能性来自于化学修饰胞嘧啶以扩大基因组潜力的酶。一些修饰改变了编码序列,例如通过AID/APOBEC酶使胞嘧啶脱氨基以产生免疫学或病毒学多样性。其他修饰对于表观遗传控制、改变基因表达或细胞身份至关重要。其中,与最近发现的修饰(例如通过泰特酶氧化为5-羟甲基胞嘧啶)相比,胞嘧啶甲基化是很好理解的。进一步的复杂性来自胞嘧啶去甲基化,这是一个影响细胞多能性的神秘过程。最近的见解帮助我们提出了一个完整的DNA去甲基化模型,占胞嘧啶氧化,脱氨基和碱基切除修复的贡献。总的来说,这种丰富的混合变化使胞嘧啶成为基因组的“外卡”,其依赖于环境的功能使碱基远远超过生命代码中的静态字母。
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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