title: NuRD-ZNF827 recruitment to telomeres creates a molecular scaffold for homologous recombination.
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.
authors.affiliation: 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.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Conomos
authors.affiliation: 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.
authors.forename: Roger R
authors.identifier: 0000000263026107
authors.initials: RR
authors.lastname: Reddel
authors.affiliation: 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.
authors.forename: Hilda A
authors.initials: HA
authors.lastname: Pickett
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D059765:Homologous Recombination; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C000593692:ZNF827 protein, human; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex