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. |