AI Article Synopsis
- - Human breast cancer genomes show local clusters of mutations known as "kataegis," thought to be caused by specific proteins, but evidence directly linking these proteins to kataegis is not yet established.
- - Researchers sequenced genomes of yeast mutants that express a gene associated with hypermutation from sea lamprey to analyze the mutation patterns.
- - The findings suggest that increased activity of cytosine deaminases is a significant driver of kataegis events, indicating a conserved evolutionary mechanism across species.
Article Abstract
Unlabelled: 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542020 | PMC |
| http://dx.doi.org/10.1186/1745-6150-7-47 | DOI Listing |
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