Model of telomere shortening and telomerase activity. (A) Telomere shortening. A 3′-overhang is created by the lagging strand synthesis after excision of the RNA primer resulting in a shortened telomere. 3′-synthesis of the leading strand can be carried to completion by the DNA polymerase. A 3′-overhang is created by a yet unidentified mechanism, most likely a 5′-exonuclease. After a certain number of cell divisions, telomeres become critically short and induce cellular senescence or apoptosis. (B) Telomere maintenance. Telomerase, consisting of the protein (TERT) and RNA (TERC) subunit extend telomeres by adding telomeric repeats (TTAGGG) in the 3′-direction. The DNA polymerase can then synthesize the lagging strand. This process can maintain telomere length or lead to telomere lengthening.
