Demonstration of DNA damage/repair in individual cells using in situ end labelling: association of p53 with sites of DNA damage

The Journal of Pathology
P J CoatesP A Hall

Abstract

We describe the development and application of in situ end labelling (ISEL) to identity sites of damaged DNA in the nuclei of individual cells. In cell culture, exposure to a variety of genotoxic agents induced a dose and time-dependent increase in nuclear labelling. In addition, examination of histological sections of human skin exposed to solar-stimulated UV light showed ISEL in both keratinocytes and superficial dermal cells, with the same spatial and temporal distribution as that of a marker of DNA repair, PCNA (proliferating cell nuclear antigen). Using co-localization techniques and confocal microscopy, we found increased levels of p53 in many ISEL-positive cells in vitro, with a similar distribution of labelling in the nucleus. This observation provides further evidence for a direct role of p53 in the recognition of damaged DNA. Thus, ISEL should prove a convenient method for demonstrating genotoxic insult in individual cells and in histological material, and may have value in toxicological screening. This high-resolution microscopy technique can also be used to compare the spatial distribution of various proteins implicated in the response to DNA damage with the sites of the lesion.

References

Jan 1, 1992·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·A M CassoniG G Steel
Nov 1, 1992·The Journal of Cell Biology·Y GavrieliS A Ben-Sasson
Jan 1, 1992·Archives of Dermatological Research·E BerlinginM Heenen
Nov 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·D E BrashJ Pontén
Mar 16, 1983·Biochemical and Biophysical Research Communications·K Nose, H Okamoto
Jan 1, 1993·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·J H WijsmanJ H van Dierendonck
Mar 1, 1994·Molecular and Cellular Biology·J M LarnerJ L Hamlin
Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Jan 4, 1994·Proceedings of the National Academy of Sciences of the United States of America·G BakalkinK G Wiman
Jan 14, 1994·Cell·J E Cleaver
Jul 1, 1993·Molecular and Cellular Biology·Q ZhanA J Fornace
Jun 1, 1993·Current Opinion in Cell Biology·D E BarnesB Sedgwick
Mar 1, 1993·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·C S DownesR T Johnson
Jul 1, 1993·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·R GoldH Lassmann

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Citations

Jun 1, 1996·Mutation Research·M L Smith, A J Fornace
Mar 1, 1996·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·J ThieleR Fischer
May 22, 1998·Molecular Biology of the Cell·C X CaiT F Linsenmayer
Aug 1, 1997·Neuropathology and Applied Neurobiology·R J Scott, L Hegyi
Jun 1, 1997·Molecular Pathology : MP·N J Carr, I C Talbot
Sep 1, 1995·The Journal of Clinical Investigation·G S FiresteinN J Zvaifler
Aug 19, 1997·Proceedings of the National Academy of Sciences of the United States of America·Y WuM Kulesz-Martin
Dec 7, 2007·International Journal of Radiation Biology·Eric G Wright
Dec 22, 2004·Progress in Retinal and Eye Research·Thomas F LinsenmayerJohn M Fitch
Jan 25, 2006·Journal of Autoimmunity·Bronwyn A O'BrienJan Peter Dutz
Apr 22, 1999·Arthritis and Rheumatism·G S Firestein, A M Manning
Jul 5, 2001·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·G MukherjeeM A Stanley
Mar 28, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Cindy CaiThomas Linsenmayer
Dec 17, 1997·Scandinavian Journal of Gastroenterology·R AnderssonV Soltesz
Jan 28, 1999·The Journal of Biological Chemistry·S T Szak, J A Pietenpol
Apr 30, 2002·The American Journal of Dermatopathology·Bozena Baima, Michael Sticherling
Jan 12, 2005·The Journal of Pathology·Philip J CoatesEric G Wright
Jul 9, 1999·The Journal of Pathology·J L PablosJ J Gomez-Reino
Jun 3, 2021·Pathogens·Martin A Prusinkiewicz, Joe S Mymryk
Jan 1, 1996·Current Biology : CB·J A WubahT B Knudsen
Feb 26, 2008·Experimental Cell Research·Victor V PetrovPaul J Lijnen

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