AID/APOBEC cytosine deaminase induces genome-wide kataegis

• Type of Material: Article
• Authors: Artem G. Lada, University of Nebraska Medical Center; Alok Dhar, University of Nebraska Medical Center; Robert J. Boissey, University of Nebraska Medical Center; Masa Hirano, Emory University; Aleksandr A. Rubel, Saint Petersburg University; Igor B. Rogozin, National Library of Medicine; Youri I. Pavlov, Saint Petersburg University
• Language: English
• Date: 2012-12-18
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Lada et al.; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://www.biology-direct.com/content/7/1/47
• Title of Journal or Parent Work: Biology Direct
• ISSN: 1745-6150
• Volume: 7
• Issue: 47
• Start Page: 1
• End Page: 7
• Grant/Funding Information: AGL is supported by a Graduate Research Assistantship from the University of Nebraska Medical Center (UNMC).; IBR is supported by the Intramural Research Program of the National Library of Medicine at the National Institutes of Health/DHHS.; This work was supported by UNMC Eppley Cancer Center seed grants to YIP in 2010–2011; Smoking Disease Research Program DHHS grant 2013–21 to YIP; NCI grant CA129925 to YIP; by NIH grants R01AI072435 and R01GM100151 to MDC; and by the Russian federal program “Innovative scientific personnel,” State contract #8654 to YIP, Federal Grant-in-Aid Program «Human Capital for Science and Education in Innovative Russia 2009-2013».; We appreciate the partial support that the University of Nebraska Medical Center’s DNA Sequencing Core receives from the NCRR (1S10RR027754-01, 5P20RR016469, RR018788-08) and the National Institute for General Medical Science (NIGMS) (8P20GM103427, GM103471-09).; AAR is supported by a research grant from St. Petersburg University.
• Research Categories: Health Sciences, Pathology; Biology, Cell; Biology, Genetics

Abstract

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.