NuRD-ZNF827 recruitment to telomeres creates a molecular scaffold for homologous recombination

Nat Struct Mol Biol. 2014 Sep;21(9):760-70. doi: 10.1038/nsmb.2877. Epub 2014 Aug 24.

Abstract

Alternative lengthening of telomeres (ALT) is a homologous recombination (HR)-dependent mechanism for de novo synthesis of telomeric DNA in mammalian cells. Nuclear receptors are bound to the telomeres of cells that use ALT. Here we demonstrate that nuclear receptors recruit ZNF827, a zinc-finger protein of unknown function, which recruits the nucleosome remodeling and histone deacetylation (NuRD) complex via binding to an N-terminal RRK motif within ZNF827. This results in decreased shelterin binding, hypoacetylation of telomeric chromatin, enhanced telomere-telomere interactions and recruitment of HR proteins, and it is critically important for cell viability and proliferation. We propose that NuRD-ZNF827 recruitment to human telomeres causes remodeling of telomeric chromatin and creates an environment that promotes telomere-telomere recombination and integrates and controls multiple mechanistic elements of ALT activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Cycle
  • Cell Line
  • Chromatin Assembly and Disassembly
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Knockdown Techniques
  • Homologous Recombination*
  • Humans
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism*
  • Telomere / metabolism*

Substances

  • DNA-Binding Proteins
  • ZNF827 protein, human
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex