Telomere Length Dynamics in Vascular Disease: A Review

Literature search flow diagram as per PRISMA guidelines.⁶ *Excluded papers included those relevant only to non-vascular disciplines including haematology and immunology. **Largely reviews that had been expanded upon by more recent work.

The duplex structure of a telomere consisting of DNA forming a T-loop and D-loop. Several shelterin proteins bind specifically to the telomeric DNA and facilitate telomere end protection and length control.² Shelterin complex core proteins- TRF1, 2 – Telomeric repeat-binding factors; RAP1-Human repressor activator protein 1; TIN2 – TRF1–interacting protein; Accessory Binding proteins- Ku- the Ku70/Ku86 heterodimer, tank-1,tank-2- tankyrase; MRE11/RAD50/NBS1-MRN DNA detection and repair complex, hnRNPs – heterogeneous nuclear ribonucleoprotein⁶⁷.

Illustration of the ‘end replication problem’ during unidirectional DNA replication. 1. Double stranded DNA ‘unzips’ in to a replication fork to allow DNA polymerase to synthesize in the 5′→ 3′ direction. 2. Leading strand is straightforwardly synthesized as continuous DNA from parental DNA. 3. Lagging strand can only be synthesized in discontinuous fragments with requirement of a primer. 4. Gap left by primer removal at the chromosomal terminus (telomere) cannot be repaired.¹²