Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin
S Tada1, A Li, D Maiorano
1CRC Chromosome Replication Research Group, Wellcome Trust Biocentre, Dow Street University of Dundee, Dundee DD1 5EH, UK.
Abstract:
Eukaryotic replication origins are 'licensed' for replication early in the cell cycle by loading Mcm(2-7) proteins. As chromatin replicates, Mcm(2-7) are removed, thus preventing the origin from firing again. Here we report the purification of the RLF-B component of the licensing system and show that it corresponds to Cdt1. RLF-B/Cdt1 was inhibited by geminin, a protein that is degraded during late mitosis. Immunodepletion of geminin from metaphase extracts allowed them to assemble licensed replication origins. Inhibition of CDKs in metaphase stimulated origin assembly only after the depletion of geminin. These experiments suggest that geminin-mediated inhibition of RLF-B/Cdt1 is essential for repressing origin assembly late in the cell cycle of higher eukaryotes.
Related Concept Videos
Negative Regulator Molecules
Restarting Stalled Replication Forks
S-Cdk Initiates DNA Replication
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
Separation of Sister Chromatids
At the onset of anaphase, separase, a proteolytic enzyme, is...
The Spindle Assembly Checkpoint
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Meiosis II
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...


