Journal
BIOLOGY DIRECT
Volume 7, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/1745-6150-7-47
Keywords
APOBEC; Deaminase; Mutation; Kataegis; Cancer; Diploid yeast; Hypermutation
Categories
Funding
- UNMC Eppley Cancer Center
- Smoking Disease Research Program DHHS grant [2013-21]
- NCI grant [CA129925]
- NIH [R01AI072435, R01GM100151]
- Russian federal program Innovative scientific personnel, State [8654]
- Human Capital for Science and Education in Innovative Russia
- Intramural Research Program of the National Library of Medicine at the National Institutes of Health/DHHS
- University of Nebraska Medical Center (UNMC)
- St. Petersburg University
- University of Nebraska Medical Center's DNA Sequencing Core receives from the NCRR [1S10RR027754-01, 5P20RR016469, RR018788-08]
- National Institute for General Medical Science (NIGMS) [8P20GM103427, GM103471-09]
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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.
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