title: AID/APOBEC cytosine deaminase induces genome-wide kataegis.
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.
  
  
  METHODS
  This article was reviewed by: Professor Sandor Pongor, Professor Shamil R. Sunyaev, and Dr Vladimir Kuznetsov.
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Artem G
authors.initials: AG
authors.lastname: Lada
authors.forename: Alok
authors.initials: A
authors.lastname: Dhar
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Boissy
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hirano
authors.forename: Aleksandr A
authors.initials: AA
authors.lastname: Rubel
authors.forename: Igor B
authors.initials: IB
authors.lastname: Rogozin
authors.forename: Youri I
authors.initials: YI
authors.lastname: Pavlov
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D007798:Lampreys / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D009154:Mutation; D012441:Saccharomyces cerevisiae; D020539:Sequence Analysis, Protein; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase