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AID/APOBEC cytosine deaminase induces genome-wide kataegis

Artem G Lada1, Alok Dhar2, Robert J Boissy3, Masayuki Hirano4, Aleksandr A Rubel56, Igor B Rogozin78 and Youri I Pavlov15*

Author Affiliations

1 Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA

2 Department of Genetics, Cell Biology and Anatomy and Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA

3 Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA

4 Emory Vaccine Center, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA

5 Department of Genetics, Saint Petersburg University, Universitetskaya emb. 7/9, St. Petersburg, 199034, Russia

6 St. Petersburg Branch of Vavilov Institute of General Genetics, St. Petersburg, Universitetskaya emb. 7/9, St Petersburg, 199034, Russia

7 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA

8 Institute of Cytology and Genetics, Novosibirsk, Russia

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Biology Direct 2012, 7:47  doi:10.1186/1745-6150-7-47

Published: 18 December 2012

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.

Reviewers

This article was reviewed by: Professor Sandor Pongor, Professor Shamil R. Sunyaev, and Dr Vladimir Kuznetsov.

Keywords:
APOBEC; Deaminase; Mutation; Kataegis; Cancer; Diploid yeast; Hypermutation