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

T Chibazakura, K Kamachi, M Ohara… - … and Cellular Biology, 2011 - Am Soc Microbiol
T Chibazakura, K Kamachi, M Ohara, S Tane, H Yoshikawa, JM Roberts
Molecular and Cellular Biology, 2011Am Soc Microbiol
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 …
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.
American Society for Microbiology