Each round of DNA replication cannot fully copy the very end of a linear chromosome (the end-replication problem), so the double-stranded telomeric repeat tract shortens by roughly 50–200 bp per division while a short single-stranded 3′ overhang remains. The shelterin complex (TRF1/TRF2/POT1/TIN2/RAP1/TPP1) folds that overhang back to invade the duplex, forming a T-loop that physically hides the chromosome end from the cell's DNA-repair machinery.
T-loop probability: P = 1 / (1 + exp(-(D - Dc) / k))
scaled by shelterin: P_eff = P · (0.4 + 0.6·S)
DNA-damage signal: DDR → (1 - P_eff) · 100% (relaxes toward this target)
Replication loss: ΔL ≈ -(100 to 150) bp per division (+telomerase gain if active)
D is the double-stranded telomere length, Dc ≈ 1,500 bp is the critical length below which there usually isn't enough duplex left for stable strand invasion, k sets how sharply the transition happens, and S ∈ [0,1] is the shelterin level. When the T-loop can't be maintained, the exposed end is read by the cell as a double-strand break: ATM kinase and 53BP1 accumulate at the site, p53/p21 are activated, and the cell exits the cycle — replicative senescence, the cellular basis of the Hayflick limit.
- Telomere length — directly sets how much double-stranded repeat DNA remains at the chromosome end.
- Shelterin level — how much of the protective protein complex is available to stabilize the T-loop.
- Divide Cell — runs one replication cycle: the duplex shortens via the end-replication problem (and regrows if telomerase is active), advancing the division counter.
- Telomerase — the reverse-transcriptase most somatic cells silence; toggling it on (as in germline, stem, and most cancer cells) adds repeat DNA back each division instead of losing it.