Cell Cycle-dependent Regulation of the Association Between Origin Recognition Proteins and Somatic Cell Chromatin

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2002 Mar 13

PMID 11889049

Citations 26

Authors

Wei-Hsin Sun

Thomas R Coleman

Melvin L DePamphilis

Affiliations

Soon will be listed here.

Abstract

Previous studies have suggested that cell cycle-dependent changes in the affinity of the origin recognition complex (ORC) for chromatin are involved in regulating initiation of DNA replication. To test this hypothesis, chromatin lacking functional ORCs was isolated from metaphase hamster cells and incubated in Xenopus egg extracts to initiate DNA replication. Intriguingly, Xenopus ORC rapidly bound to hamster somatic chromatin in a Cdc6-dependent manner and was then released, concomitant with initiation of DNA replication. Once pre-replication complexes (pre-RCs) were assembled either in vitro or in vivo, further binding of XlORC was inhibited. Neither binding nor release of XlORC was affected by inhibitors of either cyclin-dependent protein kinase activity or DNA synthesis. In contrast, inhibition of pre-RC assembly, either by addition of Xenopus geminin or by depletion of XlMcm proteins, augmented ORC binding by inhibiting ORC release. These results demonstrate a programmed release of XlORC from somatic cell chromatin as it enters S phase, consistent with the proposed role for ORC in preventing re-initiation of DNA replication during S phase.

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References

Gillespie P, J Blow J . Nucleoplasmin-mediated chromatin remodelling is required for Xenopus sperm nuclei to become licensed for DNA replication. Nucleic Acids Res. 1999; 28(2):472-80. PMC: 102529. DOI: 10.1093/nar/28.2.472. View

Wu J, Yu G, Gilbert D . Origin-specific initiation of mammalian nuclear DNA replication in a Xenopus cell-free system. Methods. 1998; 13(3):313-24. DOI: 10.1006/meth.1997.0530. View

Li C, Bogan J, Natale D, DePamphilis M . Selective activation of pre-replication complexes in vitro at specific sites in mammalian nuclei. J Cell Sci. 2000; 113 ( Pt 5):887-98. DOI: 10.1242/jcs.113.5.887. View

Drury L, Perkins G, Diffley J . The cyclin-dependent kinase Cdc28p regulates distinct modes of Cdc6p proteolysis during the budding yeast cell cycle. Curr Biol. 2000; 10(5):231-40. DOI: 10.1016/s0960-9822(00)00355-9. View

Coverley D, Pelizon C, Trewick S, Laskey R . Chromatin-bound Cdc6 persists in S and G2 phases in human cells, while soluble Cdc6 is destroyed in a cyclin A-cdk2 dependent process. J Cell Sci. 2000; 113 ( Pt 11):1929-38. DOI: 10.1242/jcs.113.11.1929. View

Natale D, Li C, Sun W, DePamphilis M . Selective instability of Orc1 protein accounts for the absence of functional origin recognition complexes during the M-G(1) transition in mammals. EMBO J. 2000; 19(11):2728-38. PMC: 212765. DOI: 10.1093/emboj/19.11.2728. View

Jares P, J Blow J . Xenopus cdc7 function is dependent on licensing but not on XORC, XCdc6, or CDK activity and is required for XCdc45 loading. Genes Dev. 2000; 14(12):1528-40. PMC: 316685. View

Bogan J, Natale D, DePamphilis M . Initiation of eukaryotic DNA replication: conservative or liberal?. J Cell Physiol. 2000; 184(2):139-50. DOI: 10.1002/1097-4652(200008)184:2<139::AID-JCP1>3.0.CO;2-8. View

Mizushima T, Takahashi N, Stillman B . Cdc6p modulates the structure and DNA binding activity of the origin recognition complex in vitro. Genes Dev. 2000; 14(13):1631-41. PMC: 316732. View

10.

Kelly T, Brown G . Regulation of chromosome replication. Annu Rev Biochem. 2000; 69:829-80. DOI: 10.1146/annurev.biochem.69.1.829. View

11.

Petersen B, Wagener C, MARINONI F, Kramer E, Melixetian M, Lazzerini Denchi E . Cell cycle- and cell growth-regulated proteolysis of mammalian CDC6 is dependent on APC-CDH1. Genes Dev. 2000; 14(18):2330-43. PMC: 316932. DOI: 10.1101/gad.832500. View

12.

Pelizon C, Madine M, Romanowski P, Laskey R . Unphosphorylatable mutants of Cdc6 disrupt its nuclear export but still support DNA replication once per cell cycle. Genes Dev. 2000; 14(19):2526-33. PMC: 316983. DOI: 10.1101/gad.176300. View

13.

Mendez J, Stillman B . Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis. Mol Cell Biol. 2000; 20(22):8602-12. PMC: 102165. DOI: 10.1128/MCB.20.22.8602-8612.2000. View

14.

Walter J . Evidence for sequential action of cdc7 and cdk2 protein kinases during initiation of DNA replication in Xenopus egg extracts. J Biol Chem. 2000; 275(50):39773-8. DOI: 10.1074/jbc.M008107200. View

15.

Wohlschlegel J, Dwyer B, Dhar S, Cvetic C, Walter J, Dutta A . Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science. 2000; 290(5500):2309-12. DOI: 10.1126/science.290.5500.2309. View

16.

Altman A, Fanning E . The Chinese hamster dihydrofolate reductase replication origin beta is active at multiple ectopic chromosomal locations and requires specific DNA sequence elements for activity. Mol Cell Biol. 2001; 21(4):1098-110. PMC: 99564. DOI: 10.1128/MCB.21.4.1098-1110.2001. View

17.

Tada S, Li A, Maiorano D, Mechali M, J Blow J . Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin. Nat Cell Biol. 2001; 3(2):107-13. PMC: 3605706. DOI: 10.1038/35055000. View

18.

Kreitz S, Ritzi M, Baack M, Knippers R . The human origin recognition complex protein 1 dissociates from chromatin during S phase in HeLa cells. J Biol Chem. 2000; 276(9):6337-42. DOI: 10.1074/jbc.M009473200. View

19.

Nguyen V, Co C, Li J . Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature. 2001; 411(6841):1068-73. DOI: 10.1038/35082600. View

20.

J Blow J . Control of chromosomal DNA replication in the early Xenopus embryo. EMBO J. 2001; 20(13):3293-7. PMC: 125522. DOI: 10.1093/emboj/20.13.3293. View