Chen X, et al. (2012) Nucleosomes suppress spontaneous mutations base-specifically in eukaryotes. Science 335(6073):1235-8
Abstract: It is unknown how the composition and structure of DNA within the cell affect spontaneous mutations. Theory suggests that in eukaryotic genomes, nucleosomal DNA undergoes fewer C-->T mutations because of suppressed cytosine hydrolytic deamination relative to nucleosome-depleted DNA. Comparative genomic analyses and a mutation accumulation experiment showed that nucleosome occupancy nearly eliminated cytosine deamination, resulting in an ~50% decrease of the C-->T mutation rate in nucleosomal DNA. Furthermore, the rates of G-->T and A-->T mutations were also about twofold suppressed by nucleosomes. On the basis of these results, we conclude that nucleosome-dependent mutation spectra affect eukaryotic genome structure and evolution and may have implications for understanding the origin of mutations in cancers and in induced pluripotent stem cells.
|Status: Published||Type: Comparative Study | Journal Article | Research Support, Non-U.S. Gov't||PubMed ID: 22403392|
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