Involvement of WRN helicase in immortalization and tumorigenesis by the telomeric crisis pathway (Review).

[werner syndrome]

The repeated replication of cells shortens telomeres , culminating in their instability , after which most cells cease to replicate and die . However , a small fraction of the cells become immortalized by maintaining telomeres with activated telomerase activity . It has been proposed that WRN helicase encoded by the WRN gene , the causative gene of Werner syndrome (WS ), is required for immortalization by the telomeric crisis pathway (TCP ) in a system that uses lymphoblastoid cell lines transformed by the Epstein-Barr virus . Taken together , these characteristics indicate that WRN helicase is also required for the immortalization of epithelial cells by TCP and consequent carcinogenesis , suggesting that the tumorigenesis of epithelial cells by TCP is suppressed in WS lacking the WRN helicase function . Notably , in WS the pathway of alternative lengthening of telomeres without activation of telomerase activity has been suggested to be involved in immortalization and tumorigenesis . This factor is consistent with the abundance of non-epithelial cancers in WS in that the ratio of epithelial to non-epithelial cancers is approximately 1 :1 in WS patients compared to 10 :1 in the general population . A hypothetical scheme showing the role of WRN helicase in immortalization by means of the supposed 'breakage-fusion -bridge cycle ' of chromosomes at telomeric crisis is described .