In the Loop: Unusual DNA Structures at Telomeric Repeats and Their Impact on Telomere Function

Telomeric repeats recruit the shelterin complex to prevent activation of the double-strand break response at chromosome ends. Thousands of TTAGGG repeats are present at each chromosome end to ensure telomere function. This abundance of G-rich repeats comes with the propensity to generate unusual DNA structures. The telomere loop (t-loop) structure, generated by strand invasion of the 3' overhang in the internal repeats, contributes to telomere function. G4-DNA is promoted by the stretches of G-rich repeats in a single-stranded form and may affect telomere replication and elongation by telomerase. The intramolecular homology can lead to the formation of internal loops (i-loops) via intramolecular recombination at sites of telomeric damage, which can promote the excision of telomeric repeats as extrachromosomal circular DNA. Shelterin promotes t-loops, counteracting the accumulation of pathological structures either directly or via the recruitment of specialized helicases. Here, we will discuss the current evidence for the formation of unusual DNA structures at telomeres and possible implications for telomere function.