en
Scientific article
Open access
English

Alternative lengthening of human telomeres is a conservative DNA replication process with features of break‐induced replication

Published inEMBO reports, vol. 17, no. 12, p. 1731-1737
Publication date2016-10-19
First online date2016-10-19
Abstract

Human malignancies overcome replicative senescence either by activating the reverse-transcriptase telomerase or by utilizing a homologous recombination-based mechanism, referred to as alter- native lengthening of telomeres (ALT). In budding yeast, ALT exhibits features of break-induced replication (BIR), a repair pathway for one-ended DNA double-strand breaks (DSBs) that requires the non-essential subunit Pol32 of DNA polymerase delta and leads to conservative DNA replication. Here, we examined whether ALT in human cancers also exhibits features of BIR. A telomeric fluorescence in situ hybridization protocol involving three consecutive staining steps revealed the presence of conservatively replicated telomeric DNA in telomerase-negative cancer cells. Furthermore, depletion of PolD3 or PolD4, two subunits of human DNA polymerase delta that are essential for BIR, reduced the frequency of conservatively replicated telomeric DNA ends and led to shorter telomeres and chromosome end-to-end fusions. Taken together, these results suggest that BIR is associated with conservative DNA replication in human cells and mediates ALT in cancer.

eng
Keywords
  • PolD3
  • PolD4
  • Alternative lengthening of telomeres
  • Break‐induced replication
  • Telomere length regulation
Funding
  • European Commission -
  • Swiss National Science Foundation -
Citation (ISO format)
ROUMELIOTI, Fani‐Marlen et al. Alternative lengthening of human telomeres is a conservative DNA replication process with features of break‐induced replication. In: EMBO reports, 2016, vol. 17, n° 12, p. 1731–1737. doi: 10.15252/embr.201643169
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal1469-221X
14views
3downloads

Technical informations

Creation01/02/2024 3:36:25 PM
First validation01/17/2024 3:09:25 PM
Update time01/17/2024 3:09:25 PM
Status update01/17/2024 3:09:25 PM
Last indexation05/06/2024 5:46:16 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack