sorry, we can't preview this file

...but you can still download s41467-020-20819-4 (1).pdf
s41467-020-20819-4 (1).pdf (6.18 MB)

Oncogenic herpesvirus KSHV triggers hallmarks of alternative lengthening of telomeres

Download (6.18 MB)
journal contribution
posted on 22.01.2021, 14:58 by Timothy P Lippert, Paulina Marzec, Aurora I Idilli, Grzegorz Sarek, Aleksandra Vancevska, Mark Bower, Paul J Farrell, Päivi M Ojala, Niklas Feldhahn, Simon J Boulton
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.

Funding

Crick (Grant ID: 10048, Grant title: Boulton FC001048) European Research Council (Grant ID: 742437 - TelMetab, Grant title: ERC 742437 - TelMetab)

History

Licence

Exports