This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Isaac, C. E.
Right arrow Articles by Dick, F. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Isaac, C. E.
Right arrow Articles by Dick, F. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2006, p. 3659-3671, Vol. 26, No. 9
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.9.3659-3671.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Retinoblastoma Protein Regulates Pericentric Heterochromatin

Christian E. Isaac,1,3 Sarah M. Francis,1,3 Alison L. Martens,1 Lisa M. Julian,1,3 Laurie A. Seifried,1,3 Natalie Erdmann,4 Ulrich K. Binné,5 Lea Harrington,4 Piotr Sicinski,6 Nathalie G. Bérubé,2,3 Nicholas J. Dyson,5 and Frederick A. Dick1,2,3,5*

London Regional Cancer Program,1 Children's Health Research Institute,2 Department of Biochemistry, University of Western Ontario, London, Ontario, Canada,3 Campbell Family Institute for Breast Cancer Research, Toronto, Ontario, Canada,4 Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts,5 Dana-Farber Cancer Institute, Boston, Massachusetts6

Received 7 October 2005/ Returned for modification 9 November 2005/ Accepted 3 February 2006

The retinoblastoma protein (pRb) has been proposed to regulate cell cycle progression in part through its ability to interact with enzymes that modify histone tails and create a repressed chromatin structure. We created a mutation in the murine Rb1 gene that disrupted pRb's ability to interact with these enzymes to determine if it affected cell cycle control. Here, we show that loss of this interaction slows progression through mitosis and causes aneuploidy. Our experiments reveal that while the LXCXE binding site mutation does not disrupt pRb's interaction with the Suv4-20h histone methyltransferases, it dramatically reduces H4-K20 trimethylation in pericentric heterochromatin. Disruption of heterochromatin structure in this chromosomal region leads to centromere fusions, chromosome missegregation, and genomic instability. These results demonstrate the surprising finding that pRb uses the LXCXE binding cleft to control chromatin structure for the regulation of events beyond the G1-to-S-phase transition.

* Corresponding author. Mailing address: Cancer Research Labs, 790 Commissioners Road East, London, Ontario, Canada, N6A 4L6. Phone: (519) 685-8620. Fax: (519) 685-8620. E-mail: fdick{at}uwo.ca.

Molecular and Cellular Biology, May 2006, p. 3659-3671, Vol. 26, No. 9
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.9.3659-3671.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yang, H., Pesavento, J. J., Starnes, T. W., Cryderman, D. E., Wallrath, L. L., Kelleher, N. L., Mizzen, C. A. (2008). Preferential Dimethylation of Histone H4 Lysine 20 by Suv4-20. J. Biol. Chem. 283: 12085-12092 [Abstract] [Full Text]  
  • Seifried, L. A., Talluri, S., Cecchini, M., Julian, L. M., Mymryk, J. S., Dick, F. A. (2008). pRB-E2F1 Complexes Are Resistant to Adenovirus E1A-Mediated Disruption. J. Virol. 82: 4511-4520 [Abstract] [Full Text]  
  • Longworth, M. S., Herr, A., Ji, J.-Y., Dyson, N. J. (2008). RBF1 promotes chromatin condensation through a conserved interaction with the Condensin II protein dCAP-D3. Genes Dev. 22: 1011-1024 [Abstract] [Full Text]  
  • Dechat, T., Pfleghaar, K., Sengupta, K., Shimi, T., Shumaker, D. K., Solimando, L., Goldman, R. D. (2008). Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev. 22: 832-853 [Abstract] [Full Text]  
  • Srinivasan, S. V., Mayhew, C. N., Schwemberger, S., Zagorski, W., Knudsen, E. S. (2007). RB Loss Promotes Aberrant Ploidy by Deregulating Levels and Activity of DNA Replication Factors. J. Biol. Chem. 282: 23867-23877 [Abstract] [Full Text]  
  • Balsitis, S., Dick, F., Dyson, N., Lambert, P. F. (2006). Critical Roles for Non-pRb Targets of Human Papillomavirus Type 16 E7 in Cervical Carcinogenesis. Cancer Res. 66: 9393-9400 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»