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Publication : Cyclin A promotes S-phase entry via interaction with the replication licensing factor Mcm7.

First Author  Chibazakura T Year  2011
Journal  Mol Cell Biol Volume  31
Issue  2 Pages  248-55
PubMed ID  21078875 Mgi Jnum  J:169424
Mgi Id  MGI:4940956 Doi  10.1128/MCB.00630-10
Citation  Chibazakura T, et al. (2011) Cyclin A promotes S-phase entry via interaction with the replication licensing factor Mcm7. Mol Cell Biol 31(2):248-55
abstractText  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.
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