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Oxidative Medicine and Cellular Longevity
Volume 2012 (2012), Article ID 217594, 9 pages
http://dx.doi.org/10.1155/2012/217594
Research Article

Centrosome Aberrations Associated with Cellular Senescence and p53 Localization at Supernumerary Centrosomes

Division of Morphological Science, Biomedical Research Center, Saitama Medical University, 38 Morohongo, Moroyama, Iruma, Saitama 350-0495, Japan

Received 28 May 2012; Revised 27 August 2012; Accepted 11 September 2012

Academic Editor: William C. Burhans

Copyright © 2012 Susumu Ohshima. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Centrosome overduplication or amplification has been observed in many human cancers and in premalignant tissue, but the mechanisms leading to such centrosome aberrations are not fully understood. We previously showed that abnormal mitotic cells with supernumerary centrosomes increase with replicative senescence in human fibroblasts, especially in a polyploid subpopulation. This study examines localization of p53 protein at centrosomes in mitotic cells, which is often observed in association with DNA damage response, to investigate a possible association between p53 localization and numerical centrosome aberrations induced by cellular senescence. Cultures at later passages or the 4th day after exposure to H2O2 showed increased frequencies of mitotic cells with supernumerary centrosomes, especially in a polyploid subpopulation. Immunohistochemical analysis frequently showed p53-positive foci in mitotic cells, and some were localized at centrosomes. The number of p53-positive foci in mitotic cells and its localization to centrosomes increased with replicative and premature senescence. Supernumerary centrosomes showed higher frequencies of p53 localization compared to normally duplicated centrosomes. Centrosome-associated p53 protein was phosphorylated at Ser15. These data suggest a possible association between localization of p53 protein and numerical centrosome aberrations in replicatively or prematurely senescent cells.