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

Molecular mechanisms of activity and derepression of alternative lengthening of telomeres.

Author information

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.

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.

PMID:
26581522
DOI:
10.1038/nsmb.3106
[Indexed for MEDLINE]
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