Home > Research > Publications & Outputs > Characterisation of the p53-Mediated Cellular R...

Electronic data

  • journal.pone.0075800

    Rights statement: Copyright: © 2013 McFeat et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    Final published version, 2 MB, PDF document

    Available under license: CC BY

Links

Text available via DOI:

View graph of relations

Characterisation of the p53-Mediated Cellular Responses Evoked in Primary Mouse Cells Following Exposure to Ultraviolet Radiation

Research output: Contribution to journalJournal article

Published
Close
Article numbere75800
<mark>Journal publication date</mark>30/09/2013
<mark>Journal</mark>PLoS ONE
Issue number9
Volume8
Number of pages9
Publication statusPublished
Original languageEnglish

Abstract

Exposure to ultraviolet (UV) light can cause significant damage to mammalian cells and, although the spectrum of damage produced varies with the wavelength of UV, all parts of the UV spectrum are recognised as being detrimental to human health. Characterising the cellular response to different wavelengths of UV therefore remains an important aim so that risks and their moderation can be evaluated, in particular in relation to the initiation of skin cancer. The p53 tumour suppressor protein is central to the cellular response that protects the genome from damage by external agents such as UV, thus reducing the risk of tumorigenesis. In response to a variety of DNA damaging agents including UV light, wild-type p53 plays a role in mediating cell-cycle arrest, facilitating apoptosis and stimulating repair processes, all of which prevent the propagation of potentially mutagenic defects. In this study we examined the induction of p53 protein and its influence on the survival of primary mouse fibroblasts exposed to different wavelengths of UV light. UVC was found to elevate p53 protein and its sequence specific DNA binding capacity. Unexpectedly, UVA treatment failed to induce p53 protein accumulation or sequence specific DNA binding. Despite this, UVA exposure of wild-type cells induced a p53 dependent G1 cell cycle arrest followed by a wave of p53 dependent apoptosis, peaking 12 hours post-insult. Thus, it is demonstrated that the elements of the p53 cellular response evoked by exposure to UV radiation are wavelength dependent. Furthermore, the interrelationship between various endpoints is complex and not easily predictable. This has important implications not only for understanding the mode of action of p53 but also for the use of molecular endpoints in quantifying exposure to different wavelengths of UV in the context of human health protection.

Bibliographic note

Copyright: © 2013 McFeat et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.