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 Hellman, A.
Right arrow Articles by Kerem, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hellman, A.
Right arrow Articles by Kerem, B.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2000, p. 4420-4427, Vol. 20, No. 12
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Replication Delay along FRA7H, a Common Fragile Site on Human Chromosome 7, Leads to Chromosomal Instability

Asaf Hellman,1 Ayelet Rahat,1 Stephen W. Scherer,2 Ariel Darvasi,3 Lap-Chee Tsui,2 and Batsheva Kerem1,*

Department of Genetics,1 and Department of Ecology, Systematics and Evolution,3 The Life Sciences Institute, The Hebrew University, Jerusalem, Israel, and Department of Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada2

Received 5 August 1999/Accepted 10 March 2000

Common fragile sites are specific chromosomal loci that show gaps, breaks, or rearrangements in metaphase chromosomes under conditions that interfere with DNA replication. The mechanism underlying the chromosomal instability at fragile sites was hypothesized to associate with late replication time. Here, we aimed to investigate the replication pattern of the common fragile site FRA7H, encompassing 160 kb on the long arm of human chromosome 7. Using in situ hybridization on interphase nuclei, we revealed that the replication of this region is initiated relatively early, before 30% of S phase is completed. However, a high fraction (~35%) of S-phase nuclei showed allelic asynchrony, indicating that the replication of FRA7H is accomplished at different times in S phase. This allelic asynchrony is not the result of a specific replication time of each FRA7H allele. Analysis of the replication pattern of adjacent clones along FRA7H by using cell population and two-color fluorescent in situ hybridization analyses showed significant differences in the replication of adjacent clones, under normal growth condition and upon aphidicolin treatment. This pattern significantly differed from that of two nonfragile regions which showed a coordinated replication under both conditions. These results indicate that aphidicolin is enhancing an already existing difference in the replication time along the FRA7H region. Based on our replication analysis of FRA7H and on previous analysis of the common fragile site FRA3B, we suggest that delayed replication is underlying the fragility at aphidicolin-induced common fragile sites.

* Corresponding author. Mailing address: Department of Genetics, The Life Sciences Institute, The Hebrew University, Jerusalem, Israel 91904. Phone: 972-2-6585689. Fax: 972-2-6586975. E-mail: kerem{at}leonardo.ls.huji.ac.il.

Molecular and Cellular Biology, June 2000, p. 4420-4427, Vol. 20, No. 12
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Jiang, Y., Lucas, I., Young, D. J., Davis, E. M., Karrison, T., Rest, J. S., Le Beau, M. M. (2009). Common fragile sites are characterized by histone hypoacetylation. Hum Mol Genet 18: 4501-4512 [Abstract] [Full Text]  
  • Debacker, K., Kooy, R.F. (2007). Fragile sites and human disease. Hum Mol Genet 16: R150-R158 [Abstract] [Full Text]  
  • Koren, A. (2007). The role of the DNA damage checkpoint in regulation of translesion DNA synthesis. Mutagenesis 22: 155-160 [Abstract] [Full Text]  
  • Torres-Rosell, J., De Piccoli, G., Cordon-Preciado, V., Farmer, S., Jarmuz, A., Machin, F., Pasero, P., Lisby, M., Haber, J. E., Aragon, L. (2007). Anaphase Onset Before Complete DNA Replication with Intact Checkpoint Responses. Science 315: 1411-1415 [Abstract] [Full Text]  
  • Diaz-Perez, S. V., Ferguson, D. O., Wang, C., Csankovszki, G., Wang, C., Tsai, S.-C., Dutta, D., Perez, V., Kim, S., Eller, C. D., Salstrom, J., Ouyang, Y., Teitell, M. A., Kaltenboeck, B., Chess, A., Huang, S., Marahrens, Y. (2006). A Deletion at the Mouse Xist Gene Exposes Trans-effects That Alter the Heterochromatin of the Inactive X Chromosome and the Replication Time and DNA Stability of Both X Chromosomes. Genetics 174: 1115-1133 [Abstract] [Full Text]  
  • El Achkar, E., Gerbault-Seureau, M., Muleris, M., Dutrillaux, B., Debatisse, M. (2005). Premature condensation induces breaks at the interface of early and late replicating chromosome bands bearing common fragile sites. Proc. Natl. Acad. Sci. USA 102: 18069-18074 [Abstract] [Full Text]  
  • Schwartz, M., Zlotorynski, E., Goldberg, M., Ozeri, E., Rahat, A., Sage, C. l., Chen, B. P.C., Chen, D. J., Agami, R., Kerem, B. (2005). Homologous recombination and nonhomologous end-joining repair pathways regulate fragile site stability. Genes Dev. 19: 2715-2726 [Abstract] [Full Text]  
  • Glover, T. W., Arlt, M. F., Casper, A. M., Durkin, S. G. (2005). Mechanisms of common fragile site instability. Hum Mol Genet 14: R197-R205 [Abstract] [Full Text]  
  • Musio, A., Montagna, C., Mariani, T., Tilenni, M., Focarelli, M. L., Brait, L., Indino, E., Benedetti, P. A., Chessa, L., Albertini, A., Ried, T., Vezzoni, P. (2005). SMC1 involvement in fragile site expression. Hum Mol Genet 14: 525-533 [Abstract] [Full Text]  
  • Herrick, J., Conti, C., Teissier, S., Thierry, F., Couturier, J., Sastre-Garau, X., Favre, M., Orth, G., Bensimon, A. (2005). Genomic Organization of Amplified MYC Genes Suggests Distinct Mechanisms of Amplification in Tumorigenesis. Cancer Res. 65: 1174-1179 [Abstract] [Full Text]  
  • Scherer, S. W., Green, E. D. (2004). Human chromosome 7 circa 2004: a model for structural and functional studies of the human genome. Hum Mol Genet 13: R303-R313 [Abstract] [Full Text]  
  • Mulvihill, D. J., Wang, Y.-H. (2004). Two Breakpoint Clusters at Fragile Site FRA3B Form Phased Nucleosomes. Genome Res 14: 1350-1357 [Abstract] [Full Text]  
  • Zlotorynski, E., Rahat, A., Skaug, J., Ben-Porat, N., Ozeri, E., Hershberg, R., Levi, A., Scherer, S. W., Margalit, H., Kerem, B. (2003). Molecular Basis for Expression of Common and Rare Fragile Sites. Mol. Cell. Biol. 23: 7143-7151 [Abstract] [Full Text]  
  • Laronne, A., Rotkopf, S., Hellman, A., Gruenbaum, Y., Porter, A. C.G., Brandeis, M. (2003). Synchronization of Interphase Events Depends neither on Mitosis nor on cdk1. Mol. Biol. Cell 14: 3730-3740 [Abstract] [Full Text]  
  • Kost-Alimova, M., Kiss, H., Fedorova, L., Yang, Y., Dumanski, J. P., Klein, G., Imreh, S. (2003). Coincidence of synteny breakpoints with malignancy-related deletions on human chromosome 3. Proc. Natl. Acad. Sci. USA 100: 6622-6627 [Abstract] [Full Text]  
  • Bentley, L, Nakabayashi, K, Monk, D, Beechey, C, Peters, J, Birjandi, Z, Khayat, F E, Patel, M, Preece, M A, Stanier, P, Scherer, S W, Moore, G E (2003). The imprinted region on human chromosome 7q32 extends to the carboxypeptidase A gene cluster: an imprinted candidate for Silver-Russell syndrome. J. Med. Genet. 40: 249-256 [Abstract] [Full Text]  
  • Ciullo, M., Debily, M.-A., Rozier, L., Autiero, M., Billault, A., Mayau, V., El Marhomy, S., Guardiola, J., Bernheim, A., Coullin, P., Piatier-Tonneau, D., Debatisse, M. (2002). Initiation of the breakage-fusion-bridge mechanism through common fragile site activation in human breast cancer cells: the model of PIP gene duplication from a break at FRA7I. Hum Mol Genet 11: 2887-2894 [Abstract] [Full Text]  
  • Toledo, F., Coquelle, A., Svetlova, E., Debatisse, M. (2000). Enhanced flexibility and aphidicolin-induced DNA breaks near mammalian replication origins: implications for replicon mapping and chromosome fragility. Nucleic Acids Res 28: 4805-4813 [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»