Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 4149K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Alexandrow, M. G. Articles by Hamlin, J. L. Search for Related Content PubMed PubMed Citation Articles by Alexandrow, M. G. Articles by Hamlin, J. L. Related Collections Related Article Social Bookmarking                            What's this?

Chromatin decondensation in S-phase involves recruitment of Cdk2 by Cdc45 and histone H1 phosphorylation

Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908

Correspondence to Joyce L. Hamlin: jlh2d{at}virginia.edu

Cdc45 is required for initiation of DNA replication and fork progression, but its function in these processes remains unknown. We show that targeting Cdc45 to specific chromosomal sites in mammalian cells results in large-scale chromatin decondensation that strongly correlates with histone H1 phosphorylation. Cdk2 is recruited to sites of Cdc45 decondensation, and Cdk2 inhibitors reduce the level of decondensation. Targeting wild-type Cdk2, but not kinase-defective Cdk2, to chromatin is also effective at inducing decondensation involving phospho-H1. Cdc45, Cdk2, Cyclin A, and phospho-H1 associate with chromatin during S-phase, and Cdc45, Cdk2, and an active H1 kinase physically interact. Replicating DNA and phospho-H1 foci colocalize in vivo, and S-phase progression and H1 phosphorylation are directly related and Cdk2 dependent. Because Cdk2 colocalizes with replication foci and H1 regulates higher-order chromatin, we suggest a model in which Cdc45 recruits Cdk2 to replication foci, resulting in H1 phosphorylation, chromatin decondensation, and facilitation of fork progression.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

Decondensation at the fork

Rabiya S. Tuma
J. Cell Biol. 2005 168: 849. [Full Text] [PDF]

This article has been cited by other articles:

• Thiriet, C., Hayes, J. J. (2009). Linker Histone Phosphorylation Regulates Global Timing of Replication Origin Firing. J. Biol. Chem. 284: 2823-2829 [Abstract] [Full Text]  
• Kumar, S., Huberman, J. A. (2009). Checkpoint-Dependent Regulation of Origin Firing and Replication Fork Movement in Response to DNA Damage in Fission Yeast. Mol. Cell. Biol. 29: 602-611 [Abstract] [Full Text]  
• Gutiyama, L. M., da Cunha, J. P. C., Schenkman, S. (2008). Histone H1 of Trypanosoma cruzi Is Concentrated in the Nucleolus Region and Disperses upon Phosphorylation during Progression to Mitosis. Eukaryot Cell 7: 560-568 [Abstract] [Full Text]  
• Al-Kaff, N., Knight, E., Bertin, I., Foote, T., Hart, N., Griffiths, S., Moore, G. (2008). Detailed Dissection of the Chromosomal Region Containing the Ph1 Locus in Wheat Triticum aestivum: With Deletion Mutants and Expression Profiling. ANN BOT (LOND) 101: 863-872 [Abstract] [Full Text]  
• Leitch, I. J., Fay, M. F. (2008). Plant Genome Horizons: Michael Bennett's Contribution to Genome Research. ANN BOT (LOND) 101: 737-746 [Full Text]  
• Park, E. A., MacAlpine, D. M., Orr-Weaver, T. L. (2007). Inaugural Article: Drosophila follicle cell amplicons as models for metazoan DNA replication: A cyclinE mutant exhibits increased replication fork elongation. Proc. Natl. Acad. Sci. USA 104: 16739-16746 [Abstract] [Full Text]  
• Song, X., Gorovsky, M. A. (2007). Unphosphorylated H1 Is Enriched in a Specific Region of the Promoter when CDC2 Is Down-Regulated during Starvation. Mol. Cell. Biol. 27: 1925-1933 [Abstract] [Full Text]  
• Yellajoshyula, D., Brown, D. T. (2006). Global modulation of chromatin dynamics mediated by dephosphorylation of linker histone H1 is necessary for erythroid differentiation. Proc. Natl. Acad. Sci. USA 103: 18568-18573 [Abstract] [Full Text]  
• Jiang, H., Olson, M. V., Medrano, D. R., Lee, O.-H., Xu, J., Piao, Y., Alonso, M. M., Gomez-Manzano, C., Hung, M.-C., Yung, W K A., Fueyo, J. (2006). A novel CRM1-dependent nuclear export signal in adenoviral E1A protein regulated by phosphorylation. FASEB J. 20: 2603-2605 [Abstract] [Full Text]  
• Gastwirt, R. F., Slavin, D. A., McAndrew, C. W., Donoghue, D. J. (2006). Spy1 Expression Prevents Normal Cellular Responses to DNA Damage: INHIBITION OF APOPTOSIS AND CHECKPOINT ACTIVATION. J. Biol. Chem. 281: 35425-35435 [Abstract] [Full Text]  
• Liu, P., Barkley, L. R., Day, T., Bi, X., Slater, D. M., Alexandrow, M. G., Nasheuer, H.-P., Vaziri, C. (2006). The Chk1-mediated S-phase Checkpoint Targets Initiation Factor Cdc45 via a Cdc25A/Cdk2-independent Mechanism. J. Biol. Chem. 281: 30631-30644 [Abstract] [Full Text]  
• Daujat, S., Zeissler, U., Waldmann, T., Happel, N., Schneider, R. (2005). HP1 Binds Specifically to Lys26-methylated Histone H1.4, whereas Simultaneous Ser27 Phosphorylation Blocks HP1 Binding. J. Biol. Chem. 280: 38090-38095 [Abstract] [Full Text]  
• Jensen, L. H., Thougaard, A. V., Grauslund, M., Sokilde, B., Carstensen, E. V., Dvinge, H. K., Scudiero, D. A., Jensen, P. B., Shoemaker, R. H., Sehested, M. (2005). Substituted Purine Analogues Define a Novel Structural Class of Catalytic Topoisomerase II Inhibitors. Cancer Res. 65: 7470-7477 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents