Local Determinants of the Mutational Landscape of the Human Genome

Cell. 2019 Mar 21;177(1):101-114. doi: 10.1016/j.cell.2019.02.051.

Abstract

Large-scale chromatin features, such as replication time and accessibility influence the rate of somatic and germline mutations at the megabase scale. This article reviews how local chromatin structures -e.g., DNA wrapped around nucleosomes, transcription factors bound to DNA- affect the mutation rate at a local scale. It dissects how the interaction of some mutagenic agents and/or DNA repair systems with these local structures influence the generation of mutations. We discuss how this local mutation rate variability affects our understanding of the evolution of the genomic sequence, and the study of the evolution of organisms and tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chromatin / genetics*
  • Chromosome Mapping / methods
  • DNA / chemistry
  • DNA Repair / genetics
  • Evolution, Molecular
  • Genome, Human / genetics*
  • Genomics
  • Germ-Line Mutation / genetics
  • Humans
  • Mutagenesis / genetics
  • Mutation / genetics*
  • Mutation Rate
  • Nucleosomes / genetics
  • Transcription Factors / genetics

Substances

  • Chromatin
  • Nucleosomes
  • Transcription Factors
  • DNA