A Premature-Termination Mutation in the Mus musculus Cyclin-Dependent Kinase 3 Gene

• Published in: Proceedings of the National Academy of Sciences - PNAS 2001-02, Vol.98 (4), p.1682-1686
• Main Authors: Ye, Xin, Zhu, Cihui, Harper, J. Wade
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological Sciences; CDK3 protein; Cell cycle; Codon, Terminator; Complementary DNA; Cyclin-Dependent Kinase 3; Cyclin-Dependent Kinases - genetics; Cyclin-Dependent Kinases - physiology; Cyclins; DNA; DNA, Complementary; Embryonic and Fetal Development; Enzymes; Exons; Genes; Genetic mutation; Genetics; Genomics; Humans; Inbred strains; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Mutant Strains; Molecular Sequence Data; Mus musculus; Mutation; Sequence Homology, Amino Acid
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.041596198

Our understanding of the mammalian cell cycle is due in large part to the analysis of cyclin-dependent kinase (CDK) 2 and CDK4/6. These kinases are regulated by E and D type cyclins, respectively, and coordinate the G1/S-phase transition. In contrast, little is known about CDK3, a homolog of CDK2 and cell division cycle kinase 2 (CDC2). Previous studies using ectopic expression of human CDK3 suggest a role for this kinase in the G1/S-phase transition, but analysis of the endogenous kinase has been stymied by the low levels of protein present in cells and by the absence of an identifiable cyclin partner. Herein we report the presence of a single point mutation in the CDK3 gene from several Mus musculus strains commonly used in the laboratory. This mutation results in the replacement of a conserved tryptophan (Trp-187) within kinase consensus domain IX with a stop codon. The protein predicted to be encoded by this allele is truncated near the T loop, which is involved in activation by CDK-activating kinase. This mutation also deletes motif XI known to be required for kinase function and is, therefore, expected to generate a null allele. In stark contrast, CDK3 from two wild-mice species (Mus spretus and Mus mus castaneus) lack this mutation. These data indicate that CDK3 is not required for M. musculus development and suggest that any functional role played by CDK3 in the G1/S-phase transition is likely to be redundant with another CDK.