Nucleic Acids Research, Vol 26, Issue 6 1382-1389, Copyright © 1998 by Oxford University Press
C Muller, P Calsou, P Frit, C Cayrol, T Carter and B Salles
DNA-dependent protein kinase (DNA-PK), a member of the phosphatidyl-
inositol (PI)3-kinase family, is involved in the repair of DNA double-
strand breaks. Its regulatory subunit, Ku, binds to DNA and recruits the
kinase catalytic subunit (DNA-PKcs). We show here a new role of DNA- PK in
the modulation of the process of nucleotide excision repair (NER) in vivo
since, as compared with their respective parental cell lines, DNA-PK
mutants (scid , V-3 and xrs 6 cells) exhibit sensitivity to UV-C
irradiation (2.0- to 2.5-fold) and cisplatin ( approximately 3- to 4- fold)
associated with a decreased activity (40-55%) of unscheduled DNA synthesis
after UV-C irradiation. Moreover, we observed that wortmannin sensitized
parental cells in vivo when combined with either cisplatin or UV-C light,
but had no effect on the DNA-PKcs deficient scid cells. Despite a lower
repair synthesis activity (approximately 2-fold) measured in vitro with
nuclear cell extracts from DNA-PK mutants, a direct involvement of DNA-PK
in the NER reaction in vitro has not been observed. This study establishes
a regulatory function of DNA-PK in the NER process in vivo but rules out a
physical role of the complex in the repair machinery at the site of the DNA
lesion.
ARTICLES
UV sensitivity and impaired nucleotide excision repair in DNA-dependent protein kinase mutant cells
Institut de Pharmacologie et de Biologie Structurale (CNRS, UPR 9062), 205 route de Narbonne, 31077 Toulouse Cedex, France.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I. R. Powley, A. Kondrashov, L. A. Young, H. C. Dobbyn, K. Hill, I. G. Cannell, M. Stoneley, Y.-W. Kong, J. A. Cotes, G. C.M. Smith, et al. Translational reprogramming following UVB irradiation is mediated by DNA-PKcs and allows selective recruitment to the polysomes of mRNAs encoding DNA repair enzymes Genes & Dev., May 15, 2009; 23(10): 1207 - 1220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yajima, K.-J. Lee, and B. P. C. Chen ATR-Dependent Phosphorylation of DNA-Dependent Protein Kinase Catalytic Subunit in Response to UV-Induced Replication Stress Mol. Cell. Biol., October 15, 2006; 26(20): 7520 - 7528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Jensen and P. M. Glazer Cell-interdependent cisplatin killing by Ku/DNA-dependent protein kinase signaling transduced through gap junctions PNAS, April 20, 2004; 101(16): 6134 - 6139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Goudelock, K. Jiang, E. Pereira, B. Russell, and Y. Sanchez Regulatory Interactions between the Checkpoint Kinase Chk1 and the Proteins of the DNA-dependent Protein Kinase Complex J. Biol. Chem., August 8, 2003; 278(32): 29940 - 29947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Kim, S.-J. Park, and S.-H. Lee A Targeted Inhibition of DNA-Dependent Protein Kinase Sensitizes Breast Cancer Cells Following Ionizing Radiation J. Pharmacol. Exp. Ther., November 1, 2002; 303(2): 753 - 759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. McHugh, W. R. Sones, and J. A. Hartley Repair of Intermediate Structures Produced at DNA Interstrand Cross-Links in Saccharomyces cerevisiae Mol. Cell. Biol., May 15, 2000; 20(10): 3425 - 3433. [Abstract] [Full Text]
|
|
|
|
|
|
J.-S. Park, S.-J. Park, X. Peng, M. Wang, M.-A. Yu, and S.-H. Lee Involvement of DNA-dependent Protein Kinase in UV-induced Replication Arrest J. Biol. Chem., November 5, 1999; 274(45): 32520 - 32527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Frit, Y. Canitrot, C. Muller, N. Foray, P. Calsou, E. Marangoni, J. Bourhis, and B. Salles Cross-Resistance to Ionizing Radiation in a Murine Leukemic Cell Line Resistant to cis-Dichlorodiammineplatinum(II): Role of Ku Autoantigen Mol. Pharmacol., July 1, 1999; 56(1): 141 - 146. [Abstract] [Full Text]
|
|
|
|
|
|
P. Calsou, P. Frit, O. Humbert, C. Muller, D. J. Chen, and B. Salles The DNA-dependent Protein Kinase Catalytic Activity Regulates DNA End Processing by Means of Ku Entry into DNA J. Biol. Chem., March 19, 1999; 274(12): 7848 - 7856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Woodard, M. G. Anderson, and W. S. Dynan Nuclear Extracts Lacking DNA-dependent Protein Kinase Are Deficient in Multiple Round Transcription J. Biol. Chem., January 1, 1999; 274(1): 478 - 485. [Abstract] [Full Text] [PDF]
|
|