Oncogenic Herpesvirus KSHV Triggers Hallmarks of Alternative Lengthening of Telomeres

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Jan 22

PMID 33479235

Citations 13

Authors

Timothy P Lippert

Paulina Marzec

Aurora I Idilli

Grzegorz Sarek

Aleksandra Vancevska

Mark Bower

Paul J Farrell

Paivi M Ojala

Niklas Feldhahn

Simon J Boulton

Affiliations

Soon will be listed here.

Abstract

To achieve replicative immortality, cancer cells must activate telomere maintenance mechanisms to prevent telomere shortening. ~85% of cancers circumvent telomeric attrition by re-expressing telomerase, while the remaining ~15% of cancers induce alternative lengthening of telomeres (ALT), which relies on break-induced replication (BIR) and telomere recombination. Although ALT tumours were first reported over 20 years ago, the mechanism of ALT induction remains unclear and no study to date has described a cell-based model that permits the induction of ALT. Here, we demonstrate that infection with Kaposi's sarcoma herpesvirus (KSHV) induces sustained acquisition of ALT-like features in previously non-ALT cell lines. KSHV-infected cells acquire hallmarks of ALT activity that are also observed in KSHV-associated tumour biopsies. Down-regulating BIR impairs KSHV latency, suggesting that KSHV co-opts ALT for viral functionality. This study uncovers KSHV infection as a means to study telomere maintenance by ALT and reveals features of ALT in KSHV-associated tumours.

Citing Articles

A Review of Telomere Attrition in Cancer and Aging: Current Molecular Insights and Future Therapeutic Approaches.

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Identifying Protein Interactions with Viral DNA Genomes during Virus Infection.

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Effects of p53 and ATRX inhibition on telomeric recombination in aging fibroblasts.

Udroiu I, Marinaccio J, Sgura A Front Oncol. 2024; 14:1322438.

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Alternative Lengthening of Telomeres in Yeast: Old Questions and New Approaches.

Musmaker K, Wells J, Tsai M, Comeron J, Malkova A Biomolecules. 2024; 14(1).

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Break-induced replication orchestrates resection-dependent template switching.

Zhang T, Rawal Y, Jiang H, Kwon Y, Sung P, Greenberg R Nature. 2023; 619(7968):201-208.

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