Telomerase-independent maintenance of telomere length in a vertebrate

Abstract

Abstract Telomere shortening places a key limitation on cell proliferation 1 . In all vertebrates explored to date, this limitation is overcome by telomerase-dependent telomere extension. Failure to maintain telomere length results in premature ageing and functional impairments in highly replicative cell populations as telomeres erode 2 . Alternative lengthening of telomeres (ALT), a telomerase-independent mechanism, compensates for telomere loss in a subset of human cancer cell lines 2 . Here, we demonstrate that the highly regenerative newt Pleurodeles waltl lacks telomerase activity, contains telomeres distinct from all known vertebrates in both sequence and structure, and deploys ALT for physiological telomere maintenance. This constitutes the first report of telomerase-independent resolution of the end-replication problem at the whole-organism level within Chordata . One-Sentence Summary P. waltl telomere biology is distinct amongst vertebrates and uses ALT at the whole-organism level.