Endogenous DNA Damage as a Source of Genomic Instability in Cancer

Cell. 2017 Feb 9;168(4):644-656. doi: 10.1016/j.cell.2017.01.002.


Genome instability, defined as higher than normal rates of mutation, is a double-edged sword. As a source of genetic diversity and natural selection, mutations are beneficial for evolution. On the other hand, genomic instability can have catastrophic consequences for age-related diseases such as cancer. Mutations arise either from inactivation of DNA repair pathways or in a repair-competent background due to genotoxic stress from celluar processes such as transcription and replication that overwhelm high-fidelity DNA repair. Here, we review recent studies that shed light on endogenous sources of mutation and epigenomic features that promote genomic instability during cancer evolution.

Keywords: DNA damage; DNA repair; DNA replication; Genome instability; cancer; mutagenesis; transcription.

Publication types

  • Review
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / chemistry
  • DNA Damage*
  • DNA Repair
  • DNA Replication
  • Genomic Instability*
  • Humans
  • Mutation
  • Neoplasms / genetics*
  • Transcriptional Activation


  • Chromatin