This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lu, H. Articles by Lavin, M. F. Search for Related Content PubMed PubMed Citation Articles by Lu, H. Articles by Lavin, M. F.

The Radiosensitive Cell Line 180BR Is Not Defective in the Major DNA Damage-sensing Proteins¹

The Queensland Institute of Medical Research, The Bancroft Centre, Herston, Brisbane, Queensland 4029, Australia [H. L., Q. S., M. F. L.]; Medical Research Council, MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton BN1 9RR, United Kingdom [C. A.]; The Department of Surgery, University of Queensland, PO Royal Brisbane Hospital, Herston, Brisbane, Queensland 4029 Australia [M. F. L.]

The fibroblast culture 180BR, established from a patient showing an adverse response to radiotherapy, has been shown previously to be hypersensitive to ionizing radiation and to be defective in the repair of DNA double-strand breaks. We demonstrate here that the products of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and its regulatory subunits (Ku 70 and Ku 80) are present at normal levels and possess functional activity. The product of the gene mutated in the human genetic disorder ataxia-telangiectasia was also detected in these cells. Apoptosis was detected after high-dose ionizing radiation exposure, and this process was accompanied by specific degradation of DNA-PKcs, ATM, and poly(ADP-ribose) polymerase. Activation of CPP32, an interleukin 1ß converting enzyme-like protease implicated in apoptosis, was also observed in 180BR cells in response to radiation damage. The radiosensitivity observed in 180BR cells can be accounted for, at least in part, by radiation-induced apoptosis, and the defect in these cells is not a gross one in DNA-PKcs or ATM.

¹ This work was supported by grants from the Australian National Health and Medical Research Council and the Queensland Cancer Fund. H. L. was supported by a studentship from the Tzu Chi Foundation. H. L. and Q. S. contributed equally to this work.

² To whom requests for reprints should be addressed, at The Queensland Institute of Medical Research, The Bancroft Centre, 300 Herston Road, Herston, Brisbane, Queensland 4029, Australia.

Received 4/ 9/97. Accepted 10/24/97.

This article has been cited by other articles:

				H. Wang, Z.-C. Zeng, A. R. Perrault, X. Cheng, W. Qin, and G. Iliakis Genetic evidence for the involvement of DNA ligase IV in the DNA-PK-dependent pathway of non-homologous end joining in mammalian cells Nucleic Acids Res., April 15, 2001; 29(8): 1653 - 1660. [Abstract] [Full Text] [PDF]

				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]