The manuscript by Roumelioti et al. reports that break-induced replication (BIR) mediates alternative lengthening of telomeres (ALT) in human cells lacking telomerase activity. Whilst BIR has been previously implicated in maintaining ALT telomeres in yeast, the present study provides for the first time evidence that a similar mechanism acts in human cells. The authors developed a novel triple-FISH protocol, effective in differentiating semiconservative from conservative telomere replication. This pioneering approach is the only means for detection of conservative, BIR-mediated telomere replication in human cells. These results provide mechanistic insight into ALT telomere homeostasis and might lead to the development of therapies targeting human cancers that depend on ALT.
Roumelioti FM, Sotiriou SK, Katsini V, Chiourea M, Halazonetis TD, Gagos S. Alternative lengthening of human telomeres is a conservative DNA replication process with features of break-induced replication.EMBO Rep. 2016 Oct 19
The study was also selected by EMBO Reports to be represented on the Journal's cover for this volume.