Identification and functional characterization of a new member of the human Mcm protein family:: hMcm8

被引:81
作者
Gozuacik, D
Chami, M
Lagorce, D
Faivre, J
Murakami, Y
Poch, O
Biermann, E
Knippers, R
Bréchot, C
Paterlini-Bréchot, P
机构
[1] Fac Med Necker Enfants Malad, INSERM, Unit 370, Inst Pasteur, F-75730 Paris, France
[2] CNRS, Inst Biol Mol & Cellulaire, PUPR 9005, F-67084 Strasbourg, France
[3] Univ Konstanz, Dept Biol, D-78457 Constance, Germany
关键词
D O I
10.1093/nar/gkg136
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 G(1)/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 G(2)/M, phase, as for hMcm3. However, unlike hMcm3, the hMcm8 structure-bound fraction is not detectable in G(1) 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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页码:570 / 579
页数:10
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