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潜伏在基因组中的强大诱变因素。

Powerful mutators lurking in the genome.

作者信息

Petit Vincent, Vartanian Jean-Pierre, Wain-Hobson Simon

机构信息

Molecular Retrovirology Unit, CNRS URA 3015, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France.

出版信息

Philos Trans R Soc Lond B Biol Sci. 2009 Mar 12;364(1517):705-15. doi: 10.1098/rstb.2008.0272.

Abstract

The human genome encodes numerous enzymes capable of deaminating polynucleotides. While they are capable of exquisite specificity, occasionally they result in hypermutation where up to 90 per cent of cytidine or adenosine residues may be edited. As such, they constitute a formidable anti-viral barrier, for no virus can survive such a high mutation rate. As the APOBEC3 group of cytidine deaminases edit single-stranded viral DNA, the crucial question is can they hyperedit chromosomal DNA? Everything points to a positive answer. Nonetheless, hypermutants per se have not yet been described, probably being countered by highly efficient mismatch repair. For the APOBEC3 genes, not only is their physiological function unknown, but also their role in the induction of cancer remains to be determined. Yet given the pace of research, all this is certain to change in the next few years.

摘要

人类基因组编码了许多能够使多核苷酸脱氨的酶。虽然它们具有高度的特异性,但偶尔也会导致超突变,其中高达90%的胞嘧啶或腺嘌呤残基可能会被编辑。因此,它们构成了一道强大的抗病毒屏障,因为没有病毒能够在如此高的突变率下存活。由于载脂蛋白B mRNA编辑酶催化多肽样3(APOBEC3)组的胞嘧啶脱氨酶会编辑单链病毒DNA,关键问题在于它们能否对染色体DNA进行超编辑?一切迹象都指向肯定的答案。尽管如此,超突变体本身尚未被描述,可能是因为高效的错配修复机制对其进行了抵消。对于APOBEC3基因,不仅其生理功能未知,而且它们在癌症诱导中的作用仍有待确定。然而,鉴于研究的速度,在未来几年所有这些情况肯定会发生变化。

相似文献

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Powerful mutators lurking in the genome.潜伏在基因组中的强大诱变因素。
Philos Trans R Soc Lond B Biol Sci. 2009 Mar 12;364(1517):705-15. doi: 10.1098/rstb.2008.0272.

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APOBEC3A/B deletion polymorphism and cancer risk.APOBEC3A/B 缺失多态性与癌症风险。
Carcinogenesis. 2018 Feb 9;39(2):118-124. doi: 10.1093/carcin/bgx131.

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