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Oncogenic herpesvirus KSHV triggers hallmarks of alternative lengthening of telomeres.


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.

SUBMITTER: Lippert TP 

PROVIDER: S-EPMC7820467 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Oncogenic herpesvirus KSHV triggers hallmarks of alternative lengthening of telomeres.

Lippert Timothy P TP   Marzec Paulina P   Idilli Aurora I AI   Sarek Grzegorz G   Vancevska Aleksandra A   Bower Mark M   Farrell Paul J PJ   Ojala Päivi M PM   Feldhahn Niklas N   Boulton Simon J SJ  

Nature communications 20210121 1


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 de  ...[more]

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