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Nat Rev Genet. 2015 Apr;16(4):213-23. doi: 10.1038/nrg3890. Epub 2015 Mar 3.

The effects of chromatin organization on variation in mutation rates in the genome.

Author information

1
Department of Biology, Huck Institute for Genome Sciences, The Pennsylvania State University, University Park, State College, Pennsylvania 16802, USA.
2
Department of Biochemistry and Molecular Biology, Huck Institute for Genome Sciences, The Pennsylvania State University, University Park, State College, Pennsylvania 16802, USA.

Abstract

The variation in local rates of mutations can affect both the evolution of genes and their function in normal and cancer cells. Deciphering the molecular determinants of this variation will be aided by the elucidation of distinct types of mutations, as they differ in regional preferences and in associations with genomic features. Chromatin organization contributes to regional variation in mutation rates, but its contribution differs among mutation types. In both germline and somatic mutations, base substitutions are more abundant in regions of closed chromatin, perhaps reflecting error accumulation late in replication. By contrast, a distinctive mutational state with very high levels of insertions and deletions (indels) and substitutions is enriched in regions of open chromatin. These associations indicate an intricate interplay between the nucleotide sequence of DNA and its dynamic packaging into chromatin, and have important implications for current biomedical research. This Review focuses on recent studies showing associations between chromatin state and mutation rates, including pairwise and multivariate investigations of germline and somatic (particularly cancer) mutations.

PMID:
25732611
PMCID:
PMC4500049
DOI:
10.1038/nrg3890
[Indexed for MEDLINE]
Free PMC Article
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