Telomeres maintenance

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Telomere maintenance has recently been shown to depend upon WRN helicase activity. WRN is active not only as a helicase, but also as an exonuclease, and it is a very large protein (180 kD), which could in principle function as a scaffold for other factors. However, telomere maintenance has been shown to depend specifically on the DNA unwinding activity of WRN, as a point mutation that abolished helicase activity causes telomeric sequence loss. Most tellingly, loss of telomeric sequence in the absence of WRN helicase activity is specific to only one of the telomeric strands replication of the G-rich template is impaired. Coupled with evidence that WRN associates with telomeres specifically in S phase, when replication occurs, these results lead to a model in which WRN helicase activity unwinds G4 DNA formed within the G-rich template strand, to allow complete replication of telomeric sequences (Figure 8). 

Shammas MA et al. Telomere maintenance in laser capture microdissection-purified Barrett s adenocarcinoma cells and effect of telomerase inhibition in vivo. Clin Cancer Res 200S 14 4971-4980. 

Hochreiter AE et al. Telomerase template antagonist GRN163L disrupts telomere maintenance, tumor growth, and metastasis of breast cancer. Clin Cancer Res 2006 12 3184-3192. 

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