title: Nucleosomes suppress spontaneous mutations base-specifically in eukaryotes.
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.
authors.affiliation: State Key Laboratory of Bio-control, College of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Xiaoshu
authors.initials: X
authors.lastname: Chen
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Chen
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Su
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Yang
authors.forename: Fangqin
authors.initials: F
authors.lastname: Lin
authors.forename: Suhua
authors.initials: S
authors.lastname: Shi
authors.forename: Xionglei
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics*; D003596:Cytosine / Q000737:chemistry / Q000378:metabolism; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D018509:DNA, Helminth / Q000737:chemistry / Q000235:genetics; D021901:DNA, Intergenic; D003641:Deamination; D016681:Genome, Fungal; D005854:Germ Cells; D008957:Models, Genetic; D059645:Mutation Rate; D009707:Nucleosomes / Q000737:chemistry* / Q000502:physiology*; D009990:Oryzias / Q000196:embryology / Q000235:genetics*; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D012440:Saccharomyces / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D004271:DNA, Fungal; D018509:DNA, Helminth; D021901:DNA, Intergenic; D009707:Nucleosomes; D003596:Cytosine