Increased mutagenesis and unique mutation signature associated with mitotic gene conversion.

Increased mutagenesis and unique mutation signature associated with mitotic gene conversion.
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DOI:
10.1126/science.1191125
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发表时间:
2010-07-02
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Haber JE
Haber JE
中科院分区:
其他
文献类型:
--
作者:
Hicks WM;Kim M;Haber JE

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目的研究S.在酿酒酵母中,我们研究了基因转换(GC),其中两条DNA链都是新合成的。突变率比自发事件增加高达1400倍,具有显著不同的突变特征。特别突出的是微同源介导的模板开关。扩增诱导的突变在很大程度上不依赖于错配修复、Pol δ、Polη和Pol 32,而是由Polδ和Polε产生的错误引起的。这些观察结果表明,在癌基因激活的哺乳动物细胞中增加的DSB频率也可能增加获得转变为癌性状态所需的突变的可能性。
To examine the fidelity of DNA synthesis during double-strand break (DSB) repair in S. cerevisiae we studied gene conversion (GC) in which both strands of DNA are newly synthesized. The mutation rate increases up to 1400 times over spontaneous events, with a significantly different mutation signature. Especially prominent are microhomology-mediated template switches. Recombination-induced mutations are largely independent of mismatch repair, Polζ, Polη, and Pol32, but result from errors made by Polδ and Polε. These observations suggest that increased DSB frequencies in oncogene-activated mammalian cells may also increase the probability of acquiring mutations required for transition to a cancerous state.
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