Preserving genome integrity and function: the DNA damage response and histone modifications

Crit Rev Biochem Mol Biol. 2019 Jun;54(3):208-241. doi: 10.1080/10409238.2019.1620676. Epub 2019 Jun 4.

Abstract

Modulation of chromatin templates in response to cellular cues, including DNA damage, relies heavily on the post-translation modification of histones. Numerous types of histone modifications including phosphorylation, methylation, acetylation, and ubiquitylation occur on specific histone residues in response to DNA damage. These histone marks regulate both the structure and function of chromatin, allowing for the transition between chromatin states that function in undamaged condition to those that occur in the presence of DNA damage. Histone modifications play well-recognized roles in sensing, processing, and repairing damaged DNA to ensure the integrity of genetic information and cellular homeostasis. This review highlights our current understanding of histone modifications as they relate to DNA damage responses (DDRs) and their involvement in genome maintenance, including the potential targeting of histone modification regulators in cancer, a disease that exhibits both epigenetic dysregulation and intrinsic DNA damage.

Keywords: Chromatin; DNA damage; DNA double-strand break repair; genome integrity; histones; modifications; transcription.

Publication types

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

MeSH terms

  • Animals
  • Chromatin / genetics
  • DNA Damage*
  • DNA Repair*
  • Epigenesis, Genetic
  • Genomic Instability
  • Histone Code*
  • Histones / genetics
  • Humans
  • Neoplasms / genetics

Substances

  • Chromatin
  • Histones