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Mouse genomic DNA harboring the full coding sequence of cyclin G1 was cloned and analyzed. The locations of five coding exons and the intron-exon boundary sequences were found to be conserved between the mouse and the human genes. Two putative binding sites for the p53 tumor suppressor gene product were found around the first exon: one was located in the 5' regulatory region, and the other was in the first intron. The mouse cyclin G1 gene was mapped to bands A5 to B1 of chromosomes 11 (11A5-B1) by FISH using genomic DNA clone as a biotinylated probe. The location of mouse cyclin G1 is syntenic to that of its human homologue, which we previously mapped to 5q32-q34 of chromosome 5. An additional faint signal was detected on chromosome 4 (4B1-C2), probably indicating the presence of a cyclin G1-related gene or pseudogene in the mouse genome.

We previously cloned a rat cDNA encoding GAK, an association partner of cyclin G and CDK5. Here, we report the cloning of a cDNA encoding human GAK (1311 amino acids) and show that all of the unique motifs that characterize rat GAK, such as the presence of a Ser/Thr kinase domain, a tensin/auxilin homologous domain, and a Tyr phosphorylation target site, are conserved. The expression profiles of GAK and cyclin G during the synchronized HeLa cell cycle showed that GAK expression oscillates slightly, peaking at G1 phase, although the histone H1 kinase activity remains constant throughout the cell cycle. We also found that the kinase activity of immunoprecipitates of anti-cyclin G antibody fluctuates during the cell cycle with a peak at G1 phase, although the expression level of cyclin G remains almost constant. Northern blot analysis showed that GAK is expressed ubiquitously, with the highest level of expression being observed in the testis. By the FISH technique, we assigned the chromosomal localization of GAK to 4p16., (Copyright 1997 Academic Press.)