Analysis of epitope-tagged forms of the dyskeratosis congenita protein (dyskerin): Identification of a nuclear localization signal

The X-linked form of the bone marrow failure syndrome Dyskeratosis congenit a is caused by mutations in dyskerin, a 514 amino acid protein that is pres umed to play a role in ribosome biogenesis. Here we report that dyskerin ta gged with the human immunoglobulin epitope localizes to nuclei of transfect ed HeLa and COS-1 cells. A carboxyl-terminal domain consisting of amino aci ds 467-475 and encoding KKEKKKSKK is both necessary and sufficient to media te nuclear entry. Immunoglobulin-tag ed dyskerin did not interact with the Fanconi anemia group A protein, FANCA. These results suggest a nuclear role for dyskerin. Moreover, hematopoietic failure observed in both Dyskeratosi s congenita and the most common type of Fanconi anemia is unlikely to have a common mechanism resulting from abnormal physical interactions between th e respective gene products of these disorders.