Heterochromatin formation via recruitment of DNA repair proteins

Mol Biol Cell. 2015 Apr 1;26(7):1395-410. doi: 10.1091/mbc.E14-09-1413. Epub 2015 Jan 28.

Abstract

Heterochromatin formation and nuclear organization are important in gene regulation and genome fidelity. Proteins involved in gene silencing localize to sites of damage and some DNA repair proteins localize to heterochromatin, but the biological importance of these correlations remains unclear. In this study, we examined the role of double-strand-break repair proteins in gene silencing and nuclear organization. We find that the ATM kinase Tel1 and the proteins Mre11 and Esc2 can silence a reporter gene dependent on the Sir, as well as on other repair proteins. Furthermore, these proteins aid in the localization of silenced domains to specific compartments in the nucleus. We identify two distinct mechanisms for repair protein-mediated silencing-via direct and indirect interactions with Sir proteins, as well as by tethering loci to the nuclear periphery. This study reveals previously unknown interactions between repair proteins and silencing proteins and suggests insights into the mechanism underlying genome integrity.

Publication types

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

MeSH terms

  • Cell Cycle Proteins
  • Cell Nucleus / metabolism
  • Chromatin Assembly and Disassembly*
  • Chromosomes, Fungal / metabolism*
  • DNA Repair*
  • Endodeoxyribonucleases / metabolism
  • Exodeoxyribonucleases / metabolism
  • Gene Silencing
  • Heterochromatin / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Nuclear Proteins / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism*

Substances

  • Cell Cycle Proteins
  • Esc2 protein, S cerevisiae
  • Heterochromatin
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Protein Serine-Threonine Kinases
  • TEL1 protein, S cerevisiae
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • MRE11 protein, S cerevisiae