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Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin
Open accessAbstract
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.
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Citations
Cited by
DNA Replication in Eukaryotic Cells
Bell, S. P., & Dutta, A. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.110601.135425 · Cited by 2,060
The anaphase promoting complex/cyclosome: a machine designed to destroy
Peters, J.-M. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1988 · Cited by 1,315
Edgar, B. A., & Orr-Weaver, T. L. (2001) · Cell · doi:10.1016/s0092-8674(01)00334-8 · Cited by 846
DNA replication origin activation in space and time
Fragkos, M., Ganier, O., Coulombe, P., & Méchali, M. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4002 · Cited by 543
Self-citationRegulation of Early Events in Chromosome Replication
Diffley, J. F. X. (2004) · Current Biology · doi:10.1016/j.cub.2004.09.019 · Cited by 386
Metadata
- Authors
- Tada, S., Li, A., Maiorano, D., Méchali, M., & Blow, J. J.
- Venue
- Nature Cell Biology
- Published
- 2001-02
- Volume
- 3
- Issue
- 2
- Pages
- 107-113
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2128056082
- Cited by
- 456
- References
- 0
- FWCI
- 17.26
- Type
- journal article
- Language
- en
- Open access
- green
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- Tada, S., Li, A., Maiorano, D., Méchali, M., & Blow, J. J. (2001). Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin. Nature Cell Biology. https://doi.org/10.1038/35055000
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