Format

Send to

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

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

Author information

1
1] Telomere Length Regulation Group, Children's Medical Research Institute, Westmead, New South Wales, Australia. [2] Sydney Medical School, University of Sydney, New South Wales, Australia.
2
1] Sydney Medical School, University of Sydney, New South Wales, Australia. [2] Cancer Research Unit, Children's Medical Research Institute, Westmead, New South Wales, Australia.

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.

PMID:
25150861
DOI:
10.1038/nsmb.2877
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center