ABSTRACT: The X-linked form of the bone marrow failure syndrome Dyskeratosis congenita is caused by mutations in dyskerin, a 514 amino acid protein that is presumed to play a role in ribosome biogenesis. Here we report that dyskerin tagged with the human immunoglobulin epitope localizes to nuclei of transfected HeLa and COS-1 cells. A carboxyl-terminal domain consisting of amino acids 467-475 and encoding KKEKKKSKK is both necessary and sufficient to mediate nuclear entry. Immunoglobulin-tagged 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 Dyskeratosis congenita and the most common type of Fanconi anemia is unlikely to have a common mechanism resulting from abnormal physical interactions between the respective gene products of these disorders.

Keywords: Dyskeratosis congenita, hematopoietic failure, Fanconi anemia, subcellular localization.

Reprint requests to: Hagop Youssoufian, M.D., Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, fax: (713) 798-5386, e-mail: hagopy@bcm.tmc.edu.