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Molecular and Cellular Biology, July 1999, p. 5096-5105, Vol. 19, No. 7
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Atm Inactivation Results in Aberrant Telomere Clustering during Meiotic Prophase

Tej K. Pandita,1,* Christoph H. Westphal,2 Melanie Anger,3 Satin G. Sawant,1 Charles R. Geard,1 Raj K. Pandita,4 and Harry Scherthan3

Columbia University, New York, New York 100321; Harvard Medical School, Boston, Massachusetts 021152; University of Kaiserslautern, D-67653 Kaiserslautern, Germany3; and Albert Einstein College of Medicine, Bronx, New York 104614

Received 10 February 1999/Returned for modification 1 April 1999/Accepted 13 April 1999

A-T (ataxia telangiectasia) individuals frequently display gonadal atrophy, and Atm-/- mice show spermatogenic failure due to arrest at prophase of meiosis I. Chromosomal movements take place during meiotic prophase, with telomeres congregating on the nuclear envelope to transiently form a cluster during the leptotene/zygotene transition (bouquet arrangement). Since the ATM protein has been implicated in telomere metabolism of somatic cells, we have set out to investigate the effects of Atm inactivation on meiotic telomere behavior. Fluorescent in situ hybridization and synaptonemal complex (SC) immunostaining of structurally preserved spermatocytes I revealed that telomere clustering occurs aberrantly in Atm-/- mice. Numerous spermatocytes of Atm-/- mice displayed locally accumulated telomeres with stretches of SC near the clustered chromosome ends. This contrasted with spermatogenesis of normal mice, where only a few leptotene/zygotene spermatocytes I with clustered telomeres were detected. Pachytene nuclei, which were much more abundant in normal mice, displayed telomeres scattered over the nuclear periphery. It appears that the timing and occurrence of chromosome polarization is altered in Atm-/- mice. When we examined telomere-nuclear matrix interactions in spermatocytes I, a significant difference was observed in the ratio of soluble versus matrix-associated telomeric DNA sequences between meiocytes of Atm-/- and control mice. We propose that the severe disruption of spermatogenesis during early prophase I in the absence of functional Atm may be partly due to altered interactions of telomeres with the nuclear matrix and distorted meiotic telomere clustering.

* Corresponding author. Mailing address: Center for Radiological Research, College of Physicians and 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, July 1999, p. 5096-5105, Vol. 19, No. 7
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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