This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
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 Ruis, B. L.
Right arrow Articles by Hendrickson, E. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ruis, B. L.
Right arrow Articles by Hendrickson, E. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2008, p. 6182-6195, Vol. 28, No. 20
0270-7306/08/$08.00+0     doi:10.1128/MCB.00355-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Catalytic Subunit of DNA-Dependent Protein Kinase Regulates Proliferation, Telomere Length, and Genomic Stability in Human Somatic Cells {triangledown} ,{dagger}

Brian L. Ruis, Kazi R. Fattah, and Eric A. Hendrickson*

Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Received 2 March 2008/ Returned for modification 15 April 2008/ Accepted 29 July 2008

The DNA-dependent protein kinase (DNA-PK) complex is a serine/threonine protein kinase comprised of a 469-kDa catalytic subunit (DNA-PKcs) and the DNA binding regulatory heterodimeric (Ku70/Ku86) complex Ku. DNA-PK functions in the nonhomologous end-joining pathway for the repair of DNA double-stranded breaks (DSBs) introduced by either exogenous DNA damage or endogenous processes, such as lymphoid V(D)J recombination. Not surprisingly, mutations in Ku70, Ku86, or DNA-PKcs result in animals that are sensitive to agents that cause DSBs and that are also immune deficient. While these phenotypes have been validated in several model systems, an extension of them to humans has been missing due to the lack of patients with mutations in any one of the three DNA-PK subunits. The worldwide lack of patients suggests that during mammalian evolution this complex has become uniquely essential in primates. This hypothesis was substantiated by the demonstration that functional inactivation of either Ku70 or Ku86 in human somatic cell lines is lethal. Here we report on the functional inactivation of DNA-PKcs in human somatic cells. Surprisingly, DNA-PKcs does not appear to be essential, although the cell line lacking this gene has profound proliferation and genomic stability deficits not observed for other mammalian systems.

* Corresponding author. Mailing address: 6-155 Jackson Hall, Department of Biochemistry, Molecular Biology, and Biophysics, 321 Church St. SE, University of Minnesota Medical School, Minneapolis, MN 55455. Phone: (612) 624-5988. Fax: (612) 624-0426. E-mail: hendr064{at}umn.edu

{triangledown} Published ahead of print on 18 August 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, October 2008, p. 6182-6195, Vol. 28, No. 20
0270-7306/08/$08.00+0     doi:10.1128/MCB.00355-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zeitlin, S. G., Baker, N. M., Chapados, B. R., Soutoglou, E., Wang, J. Y. J., Berns, M. W., Cleveland, D. W. (2009). Double-strand DNA breaks recruit the centromeric histone CENP-A. Proc. Natl. Acad. Sci. USA 106: 15762-15767 [Abstract] [Full Text]  
  • Meek, K., Jutkowitz, A., Allen, L., Glover, J., Convery, E., Massa, A., Mullaney, T., Stanley, B., Rosenstein, D., Bailey, S. M., Johnson, C., Georges, G. (2009). SCID Dogs: Similar Transplant Potential but Distinct Intra-Uterine Growth Defects and Premature Replicative Senescence Compared with SCID Mice. J. Immunol. 183: 2529-2536 [Abstract] [Full Text]  
  • Wang, Y., Ghosh, G., Hendrickson, E. A. (2009). From the Cover: Ku86 represses lethal telomere deletion events in human somatic cells. Proc. Natl. Acad. Sci. USA 106: 12430-12435 [Abstract] [Full Text]  
  • Indiviglio, S. M., Bertuch, A. A. (2009). Ku's essential role in keeping telomeres intact. Proc. Natl. Acad. Sci. USA 106: 12217-12218 [Full Text]  
  • Schwartz, R. A., Carson, C. T., Schuberth, C., Weitzman, M. D. (2009). Adeno-Associated Virus Replication Induces a DNA Damage Response Coordinated by DNA-Dependent Protein Kinase. J. Virol. 83: 6269-6278 [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»