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AID/APOBEC cytosine deaminase induces genome-wide kataegis.


ABSTRACT:

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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.

SUBMITTER: Lada AG 

PROVIDER: S-EPMC3542020 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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AID/APOBEC cytosine deaminase induces genome-wide kataegis.

Lada Artem G AG   Dhar Alok A   Boissy Robert J RJ   Hirano Masayuki M   Rubel Aleksandr A AA   Rogozin Igor B IB   Pavlov Youri I YI  

Biology direct 20121218


<h4>Unlabelled</h4>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 induce  ...[more]

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