Heterochromatin: Guardian of the Genome

Annu Rev Cell Dev Biol. 2018 Oct 6;34:265-288. doi: 10.1146/annurev-cellbio-100617-062653. Epub 2018 Jul 25.

Abstract

Constitutive heterochromatin is a major component of the eukaryotic nucleus and is essential for the maintenance of genome stability. Highly concentrated at pericentromeric and telomeric domains, heterochromatin is riddled with repetitive sequences and has evolved specific ways to compartmentalize, silence, and repair repeats. The delicate balance between heterochromatin epigenetic maintenance and cellular processes such as mitosis and DNA repair and replication reveals a highly dynamic and plastic chromatin domain that can be perturbed by multiple mechanisms, with far-reaching consequences for genome integrity. Indeed, heterochromatin dysfunction provokes genetic turmoil by inducing aberrant repeat repair, chromosome segregation errors, transposon activation, and replication stress and is strongly implicated in aging and tumorigenesis. Here, we summarize the general principles of heterochromatin structure and function, discuss the importance of its maintenance for genome integrity, and propose that more comprehensive analyses of heterochromatin roles in tumorigenesis will be integral to future innovations in cancer treatment.

Keywords: DNA repair; chromosome segregation; constitutive heterochromatin; genome stability; pericentromeres; repetitive DNA.

Publication types

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

MeSH terms

  • Centromere / genetics
  • Chromosome Segregation / genetics
  • DNA Repair / genetics*
  • Genome / genetics
  • Genomic Instability*
  • Heterochromatin / genetics*
  • Histones / genetics
  • Humans
  • Mitosis / genetics*
  • Repetitive Sequences, Nucleic Acid / genetics
  • Telomere / genetics

Substances

  • Heterochromatin
  • Histones