How telomeres are replicated

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Abstract
Telomeres must overcome specific challenges to ensure their efficient replication. In yeast cells, telomeres are replicated in late S phase in agreement with the late firing of subtelomeric origins. By contrast, in humans, subtelomeric origins might be activated earlier, although completion of replication is resumed very late because of delayed replication fork progression at the telomeric DNA repeats. The unusual structures of telomeric chromatin hamper fork progression and may cause fork pause or arrest. We describe the events that allow the cell to alleviate these obstacles, pointing out the role of the telomeric DNA-binding proteins and of DNA-modifying enzymes. Formation of the telomere overhang is a key event in telomere replication and for telomerase recruitment and activity. We describe the different events that lead to telomerase-independent overhang formation. Overhang formation requires fork passage and the leading and the lagging strand may be processed in different ways. The erosion of telomeric DNA can be compensated for by elongation of telomeres by telomerase. We discuss the dynamic binding of telomerase and its associated proteins to telomeres during the cell cycle.