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Articles

Cyclin A Promotes S-Phase Entry via Interaction with the Replication Licensing Factor Mcm7

Taku Chibazakura, Kazuhiro Kamachi, Mayu Ohara, Shoji Tane, Hirofumi Yoshikawa, James M. Roberts
Taku Chibazakura
1Department of Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan
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  • For correspondence: taku@nodai.ac.jp
Kazuhiro Kamachi
1Department of Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan
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Mayu Ohara
1Department of Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan
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Shoji Tane
1Department of Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan
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Hirofumi Yoshikawa
1Department of Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan
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James M. Roberts
2Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98019
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DOI: 10.1128/MCB.00630-10
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ABSTRACT

Cyclin A is known to promote S-phase entry in mammals, but its critical targets in this process have not been defined. We derived a novel human cyclin A mutant (CycA-C1), which can activate cyclin-dependent kinase but cannot promote S-phase entry, and isolated replication licensing factor Mcm7 as a factor that interacts with the wild-type cyclin A but not with the mutant. We demonstrated that human cyclin A and Mcm7 interact in the chromatin fraction. To address the physiological significance of the cyclin A-Mcm7 interaction, we isolated an Mcm7 mutant (Mcm7-3) that is capable of association with CycA-C1 and found that it can also suppress the deficiency of CycA-C1 in promoting S-phase entry. Finally, RNA interference experiments showed that the CycA-C1 mutant is defective for the endogenous cyclin A function in S-phase entry and that this defect can be suppressed by the Mcm7-3 mutant. Our findings demonstrate that interaction with Mcm7 is essential for the function of cyclin A in promoting S-phase entry.

FOOTNOTES

    • Received 1 June 2010.
    • Returned for modification 19 June 2010.
    • Accepted 31 October 2010.
    • Accepted manuscript posted online 15 November 2010.
  • ↵† Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.00630-10.

  • Copyright © 2011, American Society for Microbiology
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Cyclin A Promotes S-Phase Entry via Interaction with the Replication Licensing Factor Mcm7
Taku Chibazakura, Kazuhiro Kamachi, Mayu Ohara, Shoji Tane, Hirofumi Yoshikawa, James M. Roberts
Molecular and Cellular Biology Dec 2010, 31 (2) 248-255; DOI: 10.1128/MCB.00630-10

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Cyclin A Promotes S-Phase Entry via Interaction with the Replication Licensing Factor Mcm7
Taku Chibazakura, Kazuhiro Kamachi, Mayu Ohara, Shoji Tane, Hirofumi Yoshikawa, James M. Roberts
Molecular and Cellular Biology Dec 2010, 31 (2) 248-255; DOI: 10.1128/MCB.00630-10
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