T-loop dynamics: telomere structure shapes cell fate decisions.

Abstract

Telomeres are nucleoprotein elements bound by shelterin that protect chromosome ends from DNA damage signalling and inappropriate repair. A defining architectural feature is the telomere loop (t-loop), a lariat structure formed by 3' overhang invasion into duplex telomeric DNA, which sequesters chromosome ends from damage recognition. T-loop stability is disrupted by the loss of the shelterin component TRF2, and progressive telomere shortening during ageing is predicted to compromise t-loop maintenance. In addition to intrinsic erosion, an active, shelterin-directed mechanism unwinds t-loops during mitotic arrest. This mitotic arrest-dependent telomere deprotection promotes mitotic death, requires Aurora B kinase-dependent shelterin phosphorylation and the BTR complex, and is opposed by WRN. In this review, we review how dynamic t-loop architecture integrates telomere signalling with cell fate decisions.