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Biology Direct

, 7:47

Bioinformatics

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.

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

KeywordsAPOBECDeaminaseMutationKataegisCancerDiploid yeastHypermutationAbbreviationsUNGUracil DNA glycosylase uracil-N-glycosylase

HAP6-hydroxylaminopurine

SNVSingle nucleotide variant

ssDNASingle-stranded DNA.

Electronic supplementary materialThe online version of this article doi:10.1186-1745-6150-7-47 contains supplementary material, which is available to authorized users.

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Autor: ArtemGLada - AlokDhar - RobertJBoissy - MasayukiHirano - AleksandrARubel - IgorBRogozin - YouriIPavlov

Fuente: https://link.springer.com/



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