Dyskerin and cancer: more than telomerase. The defect in mRNA translation helps in explaining how a proliferative defect leads to cancer.

Point mutations in the DKC1 gene that encodes dyskerin cause the rare inherited syndrome called X-linked dyskeratosis congenita, characterized by a failure of proliferating tissues and increased susceptibility to cancer. Dyskerin is a nucleolar protein with different functions, all fundamental to basic cellular events such as protein expression, growth, and proliferation. The two best-characterized dyskerin activities are the stabilization of the telomerase RNA component, allowing the proper function telomerase enzymatic complex, and the modification of specific uridine residues of ribosomal RNA by converting them to pseudouridine, thus allowing proper ribosome processing and function. In light of the recent findings, this review focuses on the molecular pathogenesis of dyskeratosis congenita, discussing how a defect in ribosomal function might impact on the translation of a subset of mRNAs encoding for tumour suppressors, thus providing an explanation for the apparent paradox of dyskeratosis congenita in which reduced cell proliferation is associated with cancer susceptibility. In addition, the current evidence pointing to a role played by dyskerin in tumours in the general population is also discussed.