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

Author: Pickett HA1, Reddel RR2.
Affiliation: 1Telomere Length Regulation Group, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia. 2Cancer Research Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.
Conference/Journal: Nat Struct Mol Biol.
Date published: 2015 Nov
Other: Volume ID: 22 , Issue ID: 11 , Pages: 875-80 , Special Notes: doi: 10.1038/nsmb.3106. , Word Count: 81



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