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Molecular and Cellular Biology, October 1999, p. 6963-6971, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Altered Telomere Nuclear Matrix Interactions and
Nucleosomal Periodicity in Ataxia Telangiectasia Cells before and after
Ionizing Radiation Treatment
Lubomir B.
Smilenov,
Sonu
Dhar, and
Tej K.
Pandita*
Center for Radiological Research, College of
Physicians and Surgeons, Columbia University, New York, New York
10032
Received 4 April 1999/Returned for modification 24 May
1999/Accepted 14 July 1999
Cells derived from ataxia telangiectasia (A-T) patients show a
prominent defect at chromosome ends in the form of chromosome end-to-end associations, also known as telomeric associations, seen at
G1, G2, and metaphase. Recently, we have shown
that the ATM gene product, which is defective in the
cancer-prone disorder A-T, influences chromosome end associations and
telomere length. A possible hypothesis explaining these results is that
the defective telomere metabolism in A-T cells are due to altered
interactions between the telomeres and the nuclear matrix. We examined
these interactions in nuclear matrix halos before and after radiation treatment. A difference was observed in the ratio of soluble versus matrix-associated telomeric DNA between cells derived from A-T and
normal individuals. Ionizing radiation treatment affected the ratio of
soluble versus matrix-associated telomeric DNA only in the A-T cells.
To test the hypothesis that the ATM gene product is
involved in interactions between telomeres and the nuclear matrix, we
examined such interactions in human cells expressing either a
dominant-negative effect or complementation of the ATM gene. The phenotype of RKO colorectal tumor cells expressing ATM fragments containing a leucine zipper motif mimics the altered interactions of telomere and nuclear matrix similar to that of A-T
cells. A-T fibroblasts transfected with wild-type ATM gene had corrected telomere-nuclear matrix interactions. Further, we found
that A-T cells had different micrococcal nuclease digestion patterns
compared to normal cells before and after irradiation, indicating
differences in nucleosomal periodicity in telomeres. These results
suggest that the ATM gene influences the interactions between telomeres and the nuclear matrix, and alterations in telomere chromatin could be at least partly responsible for the pleiotropic phenotypes of the ATM gene.
*
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 1999, p. 6963-6971, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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