FIGURE 1.

Modern telomeres and their proposed t-loop precursor. (A) Current telomeres require a telomerase that synthesizes the telomeric repeats and counteracts the end-replication problem. They also require telomere specific proteins that recognize the telomerase products at chromosome ends and protect the ends from the DNA damage response (solving the end-protection problem). (B) Mammalian telomeres form t-loops, which sequester the telomere end and prevent ligation by NHEJ. Telomeric proteins (blue, e.g., TRF2) are needed to form the t-loop structure. Telomeric proteins also protect telomeres from other DNA repair pathways and prevent the activation of the DNA damage signaling pathways (not shown). (C) The t-loop based primordial telomere. The proposed precursor to modern telomeres is a t-loop structure as depicted. The critical aspect of the t-loop is the strand-invasion (mediated by homologous recombination factors) of the telomere end into a repeated homologous sequence (gray box). The invaded repeat could either be close to the end or chromosome-internal. Any repetitive sequence of sufficient length to allow homologous recombination can fulfill this function. Although the strand-invasion would require a 3′ overhang, recruitment of a replisome and DNA synthesis would generate a structure lacking single-stranded DNA (shown on the left). The strand-invasion of the end blocks NHEJ and ssDNA recognition systems (e.g., SOS response), thus solving the end-protection problem. When the terminal sequences is extended by DNA replication, the end-replication problem is solved (right).