Mol. Cell：束状突变常发生在长单链DNA区

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突变通常被认为是一个随机的独立的事件。而近日发表在<em>Molecular Cell</em>的一项研究结果认为酵母和人类肿瘤中的束状突变（clustered mutation）不是随机的，常发生在长单链DNA区域。

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对慢性烷基化损伤的酵母进行测序发现束状突变可达200kb，而突变位点大多在双链断裂和复制叉处的长单链DNA。

在已测序的人类肿瘤中也发现了相似的特征，突变的胞嘧啶和鸟嘌呤常常位于基因重组时的DNA链断裂处。APOBEC家族胞嘧啶脱氨酶的靶点大都为单链DNA，其突变位点也异常丰富。

结果表明，同时发生的多种突变可以促进肿瘤的发生，也可促进进化。分析束状突变也可为解开癌症复杂的机制提供有效手段. 
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doi:10.1016/j.molcel.2012.03.030
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<br/><strong>Clustered Mutations in Yeast and in Human Cancers Can Arise from Damaged Long Single-Strand DNA Regions</strong><br/>


Steven A. Roberts, Joan Sterling, Cole Thompson, Shawn Harris, Deepak
Mav, Ruchir Shah, Leszek J. Klimczak, Gregory V. Kryukov, Ewa Malc, Piotr A. Mieczkowski, Michael A. Resnick, Dmitry A. Gordenin

Mutations are typically perceived as random, independent events. We describe here nonrandom clustered mutations in yeast and in human cancers. Genome sequencing of yeast grown under chronic alkylation damage identified mutation clusters that extend up to 200 kb. A predominance of “strand-coordinated” changes of either cytosines or guanines in the same strand, mutation patterns, and genetic controls indicated that simultaneous mutations were generated by base alkylation in abnormally long single-strand DNA (ssDNA) formed at double-strand breaks (DSBs) and replication forks. Significantly, we found mutation clusters with analogous features in sequenced human cancers. Strand-coordinated clusters of mutated cytosines or guanines often resided near chromosome rearrangement breakpoints and were highly enriched with a motif targeted by APOBEC family cytosine-deaminases, which strongly prefer ssDNA. These data indicate that hypermutation via multiple simultaneous changes in randomly formed ssDNA is a general phenomenon that may be an important mechanism producing rapid genetic variation.
<div> <br/>来源：生物谷</div>
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