Somatic and Germline Mutation Periodicity Follow the Orientation of the DNA Minor Groove around Nucleosomes.
Mutation rates along the genome are highly variable and influenced by several chromatin features. Here, we addressed how nucleosomes, the most pervasive chromatin structure in eukaryotes, affect the generation of mutations. We discovered that within nucleosomes, the somatic mutation rate across several tumor cohorts exhibits a strong 10 base pair (bp) periodicity. This periodic pattern tracks the alternation of the DNA minor groove facing toward and away from the histones. The strength and phase of the mutation rate periodicity are determined by the mutational processes active in tumors. We uncovered similar periodic patterns in the genetic variation among human and Arabidopsis populations, also detectable in their divergence from close species, indicating that the same principles underlie germline and somatic mutation rates. We propose that differential DNA damage and repair processes dependent on the minor groove orientation in nucleosome-bound DNA contribute to the 10-bp periodicity in AT/CG content in eukaryotic genomes.
['Pich|Oriol|O|', 'Muiños|Ferran|F|', 'Sabarinathan|Radhakrishnan|R|', 'Reyes-Salazar|Iker|I|', 'Gonzalez-Perez|Abel|A|', 'Lopez-Bigas|Nuria|N|']
D017360:Arabidopsis D004247:DNA D020862:GC Rich Sequence D014644:Genetic Variation D018095:Germ-Line Mutation D059645:Mutation Rate D009690:Nucleic Acid Conformation D009707:Nucleosomes
somatic mutations DNA damage DNA repair WW periodicity germline variability nucleosome positioning tumor mutations