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 Scherthan, H.
Right arrow Articles by Pandita, T. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Scherthan, H.
Right arrow Articles by Pandita, T. K.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2000, p. 7773-7783, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Meiotic Telomere Distribution and Sertoli Cell Nuclear Architecture Are Altered in Atm- and Atm-p53-Deficient Mice

Harry Scherthan,1 Martin Jerratsch,1 Sonu Dhar,2 Y. Alan Wang,3 Stephen P. Goff,2 and Tej K. Pandita2,*

University of Kaiserslautern, D-67653 Kaiserslautern, Germany1; Columbia University, New York, New York 100322; and Harvard Medical School, Boston, Massachusetts3

Received 31 January 2000/Returned for modification 20 June 2000/Accepted 18 July 2000

The ataxia telangiectasia mutant (ATM) protein is an intrinsic part of the cell cycle machinery that surveys genomic integrity and responses to genotoxic insult. Individuals with ataxia telangiectasia as well as Atm-/- mice are predisposed to cancer and are infertile due to spermatogenesis disruption during first meiotic prophase. Atm-/- spermatocytes frequently display aberrant synapsis and clustered telomeres (bouquet topology). Here, we used telomere fluorescent in situ hybridization and immunofluorescence (IF) staining of SCP3 and testes-specific histone H1 (H1t) to spermatocytes of Atm- and Atm-p53-deficient mice and investigated whether gonadal atrophy in Atm-null mice is associated with stalling of telomere motility in meiotic prophase. SCP3-H1t IF revealed that most Atm-/- p53-/- spermatocytes degenerated during late zygotene, while a few progressed to pachytene and diplotene and some even beyond metaphase II, as indicated by the presence of a few round spermatids. In Atm-/- p53-/- meiosis, the frequency of spermatocytes I with bouquet topology was elevated 72-fold. Bouquet spermatocytes with clustered telomeres were generally void of H1t signals, while mid-late pachytene and diplotene Atm-/- p53-/- spermatocytes displayed expression of H1t and showed telomeres dispersed over the nuclear periphery. Thus, it appears that meiotic telomere movements occur independently of ATM signaling. Atm inactivation more likely leads to accumulation of spermatocytes I with bouquet topology by slowing progression through initial stages of first meiotic prophase and an ensuing arrest and demise of spermatocytes I. Sertoli cells (SECs), which contribute to faithful spermatogenesis, in the Atm mutants were found to frequently display numerous heterochromatin and telomere clusters---a nuclear topology which resembles that of immature SECs. However, Atm-/- SECs exhibited a mature vimentin and cytokeratin 8 intermediate filament expression signature. Upon IF with ATM antibodies, we observed ATM signals throughout the nuclei of human and mouse SECs, spermatocytes I, and haploid round spermatids. ATM but not H1t was absent from elongating spermatid nuclei. Thus, ATM appears to be removed from spermatid nuclei prior to the occurrence of DNA nicks which emanate as a consequence of nucleoprotamine formation.

* Corresponding author. Mailing address: Center for Radiological Research, College of Physicians & Surgeons, Columbia University, VC11-213, 630 West 168th St., New York, NY 10032. Phone: (212) 305-3911. Fax: (212) 305-3229. E-mail: tkp1{at}columbia.edu.

Molecular and Cellular Biology, October 2000, p. 7773-7783, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Pandita, T. K., Richardson, C. (2009). Chromatin remodeling finds its place in the DNA double-strand break response. Nucleic Acids Res 37: 1363-1377 [Abstract] [Full Text]  
  • Mark, M., Jacobs, H., Oulad-Abdelghani, M., Dennefeld, C., Feret, B., Vernet, N., Codreanu, C.-A., Chambon, P., Ghyselinck, N. B. (2008). STRA8-deficient spermatocytes initiate, but fail to complete, meiosis and undergo premature chromosome condensation. J. Cell Sci. 121: 3233-3242 [Abstract] [Full Text]  
  • Agarwal, M., Pandita, S., Hunt, C. R., Gupta, A., Yue, X., Khan, S., Pandita, R. K., Pratt, D., Shay, J. W., Taylor, J.-S. A., Pandita, T. K. (2008). Inhibition of Telomerase Activity Enhances Hyperthermia-Mediated Radiosensitization. Cancer Res. 68: 3370-3378 [Abstract] [Full Text]  
  • Pennarun, G., Granotier, C., Hoffschir, F., Mandine, E., Biard, D., Gauthier, L. R., Boussin, F. D. (2008). Role of ATM in the telomere response to the G-quadruplex ligand 360A. Nucleic Acids Res 36: 1741-1754 [Abstract] [Full Text]  
  • Gupta, A., Guerin-Peyrou, T. G., Sharma, G. G., Park, C., Agarwal, M., Ganju, R. K., Pandita, S., Choi, K., Sukumar, S., Pandita, R. K., Ludwig, T., Pandita, T. K. (2008). The Mammalian Ortholog of Drosophila MOF That Acetylates Histone H4 Lysine 16 Is Essential for Embryogenesis and Oncogenesis. Mol. Cell. Biol. 28: 397-409 [Abstract] [Full Text]  
  • Hunt, C. R., Pandita, R. K., Laszlo, A., Higashikubo, R., Agarwal, M., Kitamura, T., Gupta, A., Rief, N., Horikoshi, N., Baskaran, R., Lee, J.-H., Lobrich, M., Paull, T. T., Roti Roti, J. L., Pandita, T. K. (2007). Hyperthermia Activates a Subset of Ataxia-Telangiectasia Mutated Effectors Independent of DNA Strand Breaks and Heat Shock Protein 70 Status. Cancer Res. 67: 3010-3017 [Abstract] [Full Text]  
  • Takada, Y., Isono, K.-i., Shinga, J., Turner, J. M. A., Kitamura, H., Ohara, O., Watanabe, G., Singh, P. B., Kamijo, T., Jenuwein, T., Burgoyne, P. S., Koseki, H. (2007). Mammalian Polycomb Scmh1 mediates exclusion of Polycomb complexes from the XY body in the pachytene spermatocytes. Development 134: 579-590 [Abstract] [Full Text]  
  • Dantzer, F., Mark, M., Quenet, D., Scherthan, H., Huber, A., Liebe, B., Monaco, L., Chicheportiche, A., Sassone-Corsi, P., de Murcia, G., Menissier-de Murcia, J. (2006). Poly(ADP-ribose) polymerase-2 contributes to the fidelity of male meiosis I and spermiogenesis. Proc. Natl. Acad. Sci. USA 103: 14854-14859 [Abstract] [Full Text]  
  • Cohen, P. E., Pollack, S. E., Pollard, J. W. (2006). Genetic Analysis of Chromosome Pairing, Recombination, and Cell Cycle Control during First Meiotic Prophase in Mammals. Endocr. Rev. 27: 398-426 [Abstract] [Full Text]  
  • Bellani, M. A., Romanienko, P. J., Cairatti, D. A., Camerini-Otero, R. D. (2005). SPO11 is required for sex-body formation, and Spo11 heterozygosity rescues the prophase arrest of Atm-/- spermatocytes. J. Cell Sci. 118: 3233-3245 [Abstract] [Full Text]  
  • Di Giacomo, M., Barchi, M., Baudat, F., Edelmann, W., Keeney, S., Jasin, M. (2005). Distinct DNA-damage-dependent and -independent responses drive the loss of oocytes in recombination-defective mouse mutants. Proc. Natl. Acad. Sci. USA 102: 737-742 [Abstract] [Full Text]  
  • Harper, L., Golubovskaya, I., Cande, W. Z. (2004). A bouquet of chromosomes. J. Cell Sci. 117: 4025-4032 [Abstract] [Full Text]  
  • Alsheimer, M., Liebe, B., Sewell, L., Stewart, C. L., Scherthan, H., Benavente, R. (2004). Disruption of spermatogenesis in mice lacking A-type lamins. J. Cell Sci. 117: 1173-1178 [Abstract] [Full Text]  
  • Kuramochi-Miyagawa, S., Kimura, T., Ijiri, T. W., Isobe, T., Asada, N., Fujita, Y., Ikawa, M., Iwai, N., Okabe, M., Deng, W., Lin, H., Matsuda, Y., Nakano, T. (2004). Mili, a mammalian member of piwi family gene, is essential for spermatogenesis. Development 131: 839-849 [Abstract] [Full Text]  
  • Liebe, B., Alsheimer, M., Hoog, C., Benavente, R., Scherthan, H. (2004). Telomere Attachment, Meiotic Chromosome Condensation, Pairing, and Bouquet Stage Duration Are Modified in Spermatocytes Lacking Axial Elements. Mol. Biol. Cell 15: 827-837 [Abstract] [Full Text]  
  • Hunt, C. R., Dix, D. J., Sharma, G. G., Pandita, R. K., Gupta, A., Funk, M., Pandita, T. K. (2004). Genomic Instability and Enhanced Radiosensitivity in Hsp70.1- and Hsp70.3-Deficient Mice. Mol. Cell. Biol. 24: 899-911 [Abstract] [Full Text]  
  • Storlazzi, A., Tesse, S., Gargano, S., James, F., Kleckner, N., Zickler, D. (2003). Meiotic double-strand breaks at the interface of chromosome movement, chromosome remodeling, and reductional division. Genes Dev. 17: 2675-2687 [Abstract] [Full Text]  
  • Fernandez-Capetillo, O., Liebe, B., Scherthan, H., Nussenzweig, A. (2003). H2AX regulates meiotic telomere clustering. JCB 163: 15-20 [Abstract] [Full Text]  
  • MacQueen, A. J., Villeneuve, A. M. (2001). Nuclear reorganization and homologous chromosome pairing during meiotic prophase require C. elegans chk-2. Genes Dev. 15: 1674-1687 [Abstract] [Full Text]  
  • Nagele, R., Velasco, A., Anderson, W., McMahon, D., Thomson, Z, Fazekas, J, Wind, K, Lee, H (2001). Telomere associations in interphase nuclei: possible role in maintenance of interphase chromosome topology. J. Cell Sci. 114: 377-388 [Abstract]  


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