Nucleic Acids Research, Vol 26, Issue 17 3944-3948, Copyright © 1998 by Oxford University Press
P Kulesza and MR Lieber
The analysis of the role of DNA-dependent protein kinase (DNA-PK) in DNA
double-strand break repair and V(D)J recombination is based primarily on
studies of murine scid, in which only the C-terminal 2% of the protein is
deleted and the remaining 98% is expressed at levels that are within an
order of magnitude of normal. In murine scid, signal joint formation is
observed at normal levels, even though coding joint formation is reduced
over three orders of magnitude. In contrast, a closely associated protein,
Ku, is necessary for both coding and signal joint formation. Based on these
observations, a reasonable hypothesis has been that absence of the DNA-PK
protein (rather than merely its C- terminal 2% truncation) would ablate
signal joint formation along with coding joint formation. In fact, a study
of equine SCID, in which there is a much larger truncation of the DNA-PK
protein, has suggested that signal joints do fail to form. In our current
study, we have analyzed signal and coding joint formation in a malignant
glioma cell line, M059J, which was previously shown to be deficient in
DNA-PK. Our quantitative analysis shows that full-length protein levels are
reduced at least 200-fold, to a level that is undetectable, yet signal
joint formation occurs at wild-type levels. This result demonstrates that
at least this form of non-homologous DNA end joining can occur in the
absence of DNA-PK.
ARTICLES
DNA-PK is essential only for coding joint formation in V(D)J recombination
Department of Pathology, Norris Comprehensive Cancer Center, Room 5425, University of Southern California School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 9003, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Allam and D. Kabelitz TCR trans-Rearrangements: Biological Significance in Antigen Recognition vs the Role as Lymphoma Biomarker J. Immunol., May 15, 2006; 176(10): 5707 - 5712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. I. Belenkov, J.-P. Paiement, L. C. Panasci, B. P. Monia, and T. Y. K. Chow An Antisense Oligonucleotide Targeted to Human Ku86 Messenger RNA Sensitizes M059K Malignant Glioma Cells to Ionizing Radiation, Bleomycin, and Etoposide but not DNA Cross-Linking Agents Cancer Res., October 15, 2002; 62(20): 5888 - 5896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Fukumura, R. Araki, A. Fujimori, Y. Tsutsumi, A. Kurimasa, G. C. Li, D. J. Chen, K. Tatsumi, and M. Abe Signal Joint Formation Is Also Impaired in DNA-Dependent Protein Kinase Catalytic Subunit Knockout Cells J. Immunol., October 1, 2000; 165(7): 3883 - 3889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Brown and Y. Chang Metabolism of Recombination Coding Ends in scid Cells J. Immunol., April 15, 2000; 164(8): 4135 - 4142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Shin, T. Rijkers, A. Pastink, and K. Meek Analyses of TCRB Rearrangements Substantiate a Profound Deficit in Recombination Signal Sequence Joining in SCID Foals: Implications for the Role of DNA-Dependent Protein Kinase in V(D)J Recombination J. Immunol., February 1, 2000; 164(3): 1416 - 1424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.M. SEKIGUCHI, Y. GAO, Y. GU, K. FRANK, Y. SUN, J. CHAUDHURI, C. ZHU, H.-L. CHENG, J. MANIS, D. FERGUSON, et al. Nonhomologous End-joining Proteins Are Required for V(D)J Recombination, Normal Growth, and Neurogenesis Cold Spring Harb Symp Quant Biol, January 1, 1999; 64(0): 169 - 182. [Abstract] [PDF]
|
|
|
|
 |
|
 M. A. Bogue, C. Jhappan, and D. B. Roth Analysis of variable (diversity) joining recombination in DNAdependent protein kinase (DNA-PK)-deficient mice reveals DNA-PK-independent pathways for both signal and coding joint formation PNAS, December 22, 1998; 95(26): 15559 - 15564. [Abstract] [Full Text] [PDF]
|
|