19
Views
6
CrossRef citations to date
0
Altmetric
Research Article

The p53-mediated DNA damage response to ionizing radiation in fibroblasts from ataxia-without-telangiectasia patients

Pages 287-295 | Published online: 03 Jul 2009
 

Abstract

Purpose: To assess the functionality of the p53-mediated pathway, activated by the ataxia-telangiectasia gene product (ATM) in response to ionizing radiation, in cells derived from four ataxiawithout-telangiectasia patients. These patients exhibit cerebellar ataxia and cellular abnormalities that are compatible with the diagnosis of ataxia-telangiectasia (AT), but the telangiectasias normally seen in AT patients are absent. Materials and method: Protein and RNA extracts were prepared from primary fibroblast cultures non- or exposed to 5Gy of ionizing radiation in order to monitor the modulation in p53 and ATM protein levels by immunologic techniques and WAF1/Cip1 (p21) mRNA by Northern blotting. Results: A sub-optimal response in terms of increased levels of p53 and the transcriptional activation of WAF1/Cip1 (p21) was seen in the ataxia-without-telangiectasia fibroblast cultures examined over a 4h period post-irradiation when compared with normal fibroblast cultures. The ATM protein was expressed at much reduced levels in the ataxia-without-telangiectasia and the classical AT fibroblast cultures examined when compared with normal fibroblast cultures. Conclusions: Despite the milder clinical phenotypes observed in these ataxia-without-telangiectasia patients and the presence of low levels of ATM protein in the fibroblast cultures, their response to ionizing radiation quantitatively resembles that reported in fibroblast cultures established from classical AT patients.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.