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First published online February 21, 2007
doi: 10.1242/10.1242/jcs.03397

Journal of Cell Science 120, 713-721 (2007)
Published by The Company of Biologists 2007
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WRN at telomeres: implications for aging and cancer

Asha S. Multani and Sandy Chang*

Department of Molecular Genetics, U.T. M.D. Anderson Cancer Center, Houston, TX 77030, USA


Figure 1
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  		Fig. 1. (A) Telosome/shelterin complex and telomere structure. The telomere folds back onto itself to form a double-stranded t-loop and a single-stranded D-loop. This complex protects telomeres at the G2 phase of the cell cycle from inappropriate NHEJ- and HR-mediated processing of telomeric DNA. The six-component telosome/shelterin is shown schematically on the t-loop, with POT1 interacting with the D-loop. (B) During DNA replication, the presence of WRN at the replication fork is postulated to enable the replication complex to efficiently replicate telomeric DNA. (C) The presence of WRN at telomeres may facilitate unwinding of the D-loop, enabling telomerase to extend telomeres. The linear 3' overhang is probably protected by POT1.

 

Figure 2
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  		Fig. 2. G-quartet (G) formation on the lagging telomeric DNA is normally resolved by WRN (orange box), enabling efficient replication of lagging strand G-rich telomeres. In the absence of WRN, G-quartet formation on the lagging telomere leads to replication fork stalling and deletion of lagging-strand telomeres (Crabbe et al., 2004Go). The resultant dysfunctional telomeres can initiate a p53-dependent DNA-damage response, leading to premature onset of replicative senescence.

 

Figure 3
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  		Fig. 3. (A) Elevated telomere sister chromatid exchanges (T-SCEs) in G5 mTerc–/– Wrn–/– cells. Unequal T-SCE generates one sister chromatid with long telomere lengths at the expense of the other. The resulting daughter cell inheriting the shorter telomeres will undergo replicative senescence, whereas the daughter cell with longer telomeres will have increased proliferative capacity, perhaps able to maintain telomere lengths indefinitely through this ALT mechanism.

 




© The Company of Biologists Ltd 2007