Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Biol Direct. 2012 Dec 18;7:47; discussion 47. doi: 10.1186/1745-6150-7-47.
Clusters of localized hypermutation in human breast cancer genomes, named "kataegis" (from the Greek for thunderstorm), are hypothesized to result from multiple cytosine deaminations catalyzed by AID/APOBEC proteins. However, a direct link between APOBECs and kataegis is still lacking. We have sequenced the genomes of yeast mutants induced in diploids by expression of the gene for PmCDA1, a hypermutagenic deaminase from sea lamprey. Analysis of the distribution of 5,138 induced mutations revealed localized clusters very similar to those found in tumors. Our data provide evidence that unleashed cytosine deaminase activity is an evolutionary conserved, prominent source of genome-wide kataegis events.
This article was reviewed by: Professor Sandor Pongor, Professor Shamil R. Sunyaev, and Dr Vladimir Kuznetsov.
在人类乳腺癌基因组中,簇状局部突变被命名为“kataegis”(来自希腊语的雷暴),据推测是由 AID/APOBEC 蛋白催化的多个胞嘧啶脱氨酶引起的。然而,APOBEC 与 kataegis 之间的直接联系仍然缺乏。我们已经对通过表达来自海七鳃鳗的高突变酶 PmCDA1 的基因在二倍体中诱导的酵母突变体的基因组进行了测序。对 5138 个诱导突变的分布进行分析,揭示了与肿瘤中发现的非常相似的局部簇。我们的数据提供了证据表明,脱靶胞嘧啶脱氨酶活性是一种进化保守的、普遍存在的全基因组 kataegis 事件的来源。
本文由 Sandor Pongor 教授、Shamil R. Sunyaev 教授和 Vladimir Kuznetsov 博士评审。