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Influence of ATM function on telomere metabolism.

Publication ,  Journal Article
Smilenov, LB; Morgan, SE; Mellado, W; Sawant, SG; Kastan, MB; Pandita, TK
Published in: Oncogene
November 27, 1997

The ATM gene product, which is defective in the cancer-prone disorder ataxia telangiectasia, has been implicated in mitogenic signal transduction, chromosome condensation, meiotic recombination and cell cycle control. The ATM gene has homology with the TEL1 gene of yeast, mutations of which lead to shortened telomeres. To test the hypothesis that the ATM gene product is involved in telomere metabolism, we examined telomeric associations (TA), telomere length, and telomerase activity in human cells expressing either dominant-negative or complementing fragments of the ATM gene. The phenotype of RKO colorectal tumor cells expressing ATM fragments containing a leucine zipper (LZ) motif mimics that of ataxia telangiectasia (A-T) cells. These transfected RKO cells relative to transfected controls had a higher frequency of cells with TA and shortened telomeres, but no detectable change in telomerase activity. In addition, the percentage of cells with TA after gamma irradiation was higher in the transfected RKO cells with dominant negative activity of the ATM gene, compared to control cells. SV40 transformed fibroblasts derived from an A-T patient and transfected with a complementing carboxyl terminal kinase region of the ATM gene had a reduced frequency of cells with TA, with no effect on the telomere length or telomerase activity. The present studies using isogenic cells with manipulated ATM function demonstrate a role for the ATM gene product in telomere metabolism.

Duke Scholars

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

November 27, 1997

Volume

15

Issue

22

Start / End Page

2659 / 2665

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Cells, Cultured
  • Transfection
  • Telomere
  • Telomerase
  • Recombinant Proteins
  • Proteins
  • Protein Serine-Threonine Kinases
  • Oncology & Carcinogenesis
  • Metaphase
 

Citation

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MLA
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Smilenov, L. B., Morgan, S. E., Mellado, W., Sawant, S. G., Kastan, M. B., & Pandita, T. K. (1997). Influence of ATM function on telomere metabolism. Oncogene, 15(22), 2659–2665. https://doi.org/10.1038/sj.onc.1201449
Smilenov, L. B., S. E. Morgan, W. Mellado, S. G. Sawant, M. B. Kastan, and T. K. Pandita. “Influence of ATM function on telomere metabolism.Oncogene 15, no. 22 (November 27, 1997): 2659–65. https://doi.org/10.1038/sj.onc.1201449.
Smilenov LB, Morgan SE, Mellado W, Sawant SG, Kastan MB, Pandita TK. Influence of ATM function on telomere metabolism. Oncogene. 1997 Nov 27;15(22):2659–65.
Smilenov, L. B., et al. “Influence of ATM function on telomere metabolism.Oncogene, vol. 15, no. 22, Nov. 1997, pp. 2659–65. Pubmed, doi:10.1038/sj.onc.1201449.
Smilenov LB, Morgan SE, Mellado W, Sawant SG, Kastan MB, Pandita TK. Influence of ATM function on telomere metabolism. Oncogene. 1997 Nov 27;15(22):2659–2665.

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

November 27, 1997

Volume

15

Issue

22

Start / End Page

2659 / 2665

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Cells, Cultured
  • Transfection
  • Telomere
  • Telomerase
  • Recombinant Proteins
  • Proteins
  • Protein Serine-Threonine Kinases
  • Oncology & Carcinogenesis
  • Metaphase