HsMCM6: a new member of the human MCM/P1 family encodes a protein homologous to fission yeast Mis5.
BACKGROUND
The tight regulatory mechanism that prevents more than one round of chromosomal DNA replication per cell cycle is thought to require the function of Mcm/P1 proteins. We report here the structural and functional analyses of HsMcm6, a human homologue of the Mis5 of Schizosaccharomyces pombe.


RESULTS
We demonstrate here that the transcription of the HsMCM6 gene was repressed in quiescent cells but was rapidly induced at the G1/S phase by growth factor stimulation. The 5' regulatory region of the HsMCM6 gene was found to harbour four putative E2F binding motifs, and these were responsible for the promoter activity. The HsMcm6 protein level oscillated during the cell cycle, with a peak at the G1/S phase. We also showed that the cell-cycle dependent change of subcellular localization of HsMcm6 resembles those of other Mcm/P1 proteins. HsMcm6 consists of two forms, a form extractable by Nonidet P-40 and the nucleus-bound form. A demonstration of the association of HsMcm6 with HsMcm2 and HsMcm7 in vivo supports the idea that they behave as a heteromeric complex. We mapped the HsMCM6 gene at 2q12-14.


CONCLUSIONS
The results indicate that the behaviour of HsMcm6 is reminiscent of replication licensing factor like other Mcm/P1 family members.
Tsuruga
H
H
Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, Suita City, Japan.
Yabuta
N
N
Hosoya
S
S
Tamura
K
K
Endo
Y
Y
Nojima
H
H
D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D005656:Fungal Proteins / Q000235:genetics*; D016193:G1 Phase / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D064151:Minichromosome Maintenance Complex Component 6; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D012045:Regulatory Sequences, Nucleic Acid; D016196:S Phase / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D029702:Schizosaccharomyces pombe Proteins; C103258:MCM6 protein, human; D064151:Minichromosome Maintenance Complex Component 6; C092300:mcm6 protein, S pombe