Oncogenic herpesvirus KSHV triggers hallmarks of alternative lengthening of telomeres.
Nat Commun
; 12(1): 512, 2021 01 21.
Article
em En
| MEDLINE
| ID: mdl-33479235
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Telômero
/
Encurtamento do Telômero
/
Homeostase do Telômero
/
Neoplasias
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article