Molecular mechanisms of activity and derepression of alternative lengthening of telomeres

Hilda A Pickett; Roger R Reddel

doi:10.1038/nsmb.3106

Molecular mechanisms of activity and derepression of alternative lengthening of telomeres

Nat Struct Mol Biol. 2015 Nov;22(11):875-80. doi: 10.1038/nsmb.3106. Epub 2015 Nov 4.

Authors

Hilda A Pickett¹, Roger R Reddel²

Affiliations

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

PMID: 26581522
DOI: 10.1038/nsmb.3106

Abstract

Alternative lengthening of telomeres (ALT) involves homology-directed telomere synthesis. This multistep process is facilitated by loss of the ATRX or DAXX chromatin-remodeling factors and by abnormalities of the telomere nucleoprotein architecture, including altered DNA sequence and decreased TRF2 saturation. Induction of telomere-specific DNA damage triggers homology-directed searches, and NuRD-ZNF827 protein-protein interactions provide a platform for the telomeric recruitment of homologous recombination (HR) proteins. Telomere lengthening proceeds by strand exchange and template-driven DNA synthesis, which culminates in dissolution of HR intermediates.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

DNA Helicases / metabolism
Homologous Recombination
Nuclear Proteins / metabolism
Telomere / metabolism*
Telomere Homeostasis*

Substances

Nuclear Proteins
DNA Helicases