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

58 Citations (Scopus)

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

Fingerprint

cytosine deaminase
Cytosine Deaminase
aid
Genome
genome
Genes
Petromyzon
Petromyzon marinus
deamination
Deamination
cytosine
Cytosine
thunderstorm
Diploidy
Breast Cancer
Thunderstorms
mutagenesis
Mutant
tumor
Yeast

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

Cite this

AID/APOBEC cytosine deaminase induces genome-wide kataegis. / Lada, Artem G.; Dhar, Alok; Boissy, Robert J; Hirano, Masayuki; Rubel, Aleksandr A.; Rogozin, Igor B.; Pavlov, Youri I.

In: Biology direct, Vol. 7, 47, 18.12.2012.

Research output: Contribution to journalArticle

Lada, Artem G. ; Dhar, Alok ; Boissy, Robert J ; Hirano, Masayuki ; Rubel, Aleksandr A. ; Rogozin, Igor B. ; Pavlov, Youri I. / AID/APOBEC cytosine deaminase induces genome-wide kataegis. In: Biology direct. 2012 ; Vol. 7.
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