Nucleic Acids Research, 2003, Vol. 31, No. 2 570-579
© 2003 Oxford University Press
Identification and functional characterization of a new member of the human Mcm protein family: hMcm8
INSERM Unit 370/Pasteur Institute, Faculté de Médecine Necker-Enfants Malades, 156 rue de Vaugirard, 75730, Paris, France, 1 PUPR 9005 CNRS, Institut de Biologie Moléculaire et Cellulaire, 15 rue René Descartes, 67084 Strasbourg-Cédex, France and 2 Department of Biology, Universität Konstanz, D-78457 Konstanz, Germany
*To whom correspondence should be addressed. Tel: +33 1 40615644; Fax: +33 1 40615581; Email: paterlini{at}necker.fr
Present addresses:
Devrim Gozuacik, Molecular Genetics Department, Weizmann Institute of Science, 76100 Rehovot, Israel
Mounia Chami, Department of Experimental and Diagnostic Medicine, Section of General Pathology, 44100 Ferrara, Italy
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
The six minichromosome maintenance proteins (Mcm2–7) are required for both the initiation and elongation of chromosomal DNA, ensuring that DNA replication takes place once, and only once, during the S phase. Here we report on the cloning of a new human Mcm gene (hMcm8) and on characterisation of its protein product. The hMcm8 gene contains the central Mcm domain conserved in the Mcm2–7 gene family, and is expressed in a range of cell lines and human tissues. hMcm8 mRNA accumulates during G1/S phase, while hMcm8 protein is detectable throughout the cell cycle. Immunoprecipitation-based studies did not reveal any participation of hMcm8 in the Mcm3/5 and Mcm2/4/6/7 subcomplexes. hMcm8 localises to the nucleus, although it is devoid of a nuclear localisation signal, suggesting that it binds to a nuclear protein. In the nucleus, the hMcm8 structure-bound fraction is detectable in S, but not in G2/M, phase, as for hMcm3. However, unlike hMcm3, the hMcm8 structure-bound fraction is not detectable in G1 phase. Overall, our data identify a new Mcm protein, which does not form part of the Mcm2–7 complex and which is only structure-bound during S phase, thus suggesting its specific role in DNA replication.
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