Distinct Modes of Telomere Synthesis and Extension Contribute to Alternative Lengthening of Telomeres

Overview

Journal iScience

Publisher Cell Press

Date 2024 Jan 12

PMID 38213617

Authors

Robert Lu

Christopher B Nelson

Samuel Rogers

Anthony J Cesare

Alexander P Sobinoff

Hilda A Pickett

Affiliations

Soon will be listed here.

Abstract

Alternative lengthening of telomeres (ALT) is a homology-directed repair mechanism that becomes activated in a subset of cancers to maintain telomere length. One of the defining features of ALT cells is the prevalence of extrachromosomal telomeric repeat (ECTR) DNA. Here, we identify that ALT cells engage in two modes of telomere synthesis. Non-productive telomere synthesis occurs during the G2 phase of the cell cycle and is characterized by newly synthesized internal telomeric regions that are not retained in the subsequent G1, coinciding with an induction of ECTR DNA. Productive telomere synthesis occurs specifically during the transition from G2 to mitosis and is defined as the extension of the telomere termini. While many proteins associated with break-induced telomere synthesis function in both non-productive and productive telomere synthesis, POLH specifically promotes productive telomere lengthening and suppresses non-productive telomere synthesis. These findings delineate the mechanism and cell cycle regulation of ALT-mediated telomere synthesis and extension.

Citing Articles

Locking the gates of immortality: targeting alternative lengthening of telomeres (ALT) pathways.

Mishra A, Patel T Med Oncol. 2025; 42(3):78.

PMID: 39964637 DOI: 10.1007/s12032-025-02627-2.

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