AID/APOBEC cytosine deaminase induces genome-wide kataegis

Artem G. Lada, Alok Dhar, Robert J. Boissy, Masayuki Hirano, Aleksandr A. Rubel, Igor B. Rogozin, Youri I. Pavlov

Research output: Contribution to journalArticle

63 Scopus citations

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.

Original languageEnglish (US)
Article number47
JournalBiology direct
Volume7
DOIs
StatePublished - Dec 18 2012

Keywords

  • APOBEC
  • Cancer
  • Deaminase
  • Diploid yeast
  • Hypermutation
  • Kataegis
  • Mutation

ASJC Scopus subject areas

  • Immunology
  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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