FIGURE 2.

Telomerase bypasses premature replicative senescence in WS fibroblasts. (A) G-quadruplexes at the lagging telomere are normally unwound by WRN helicase, making it possible to complete replication of lagging strand G-rich telomeres. (B) The absence of WRN causes stalled replication forks at the sites of unresolved G-quadruplexes at the lagging telomere, which would produce degradable substrates for factors involved in DNA repair and recombination, leading to accelerated telomere shortening. (C) Telomerase can add telomeric DNA “TTAGGG” to lagging telomeres that are lost during replication in WS cells, which overcomes the lack of WRN, enabling complete replication of lagging strand G-rich telomeres. This figure is based on reference (Multani and Chang, 2007).