Publication: Loss of poly (ADP-ribose) polymerase-2 leads to rapid development of spontaneous T-cell lymphomas in p53-deficient mice
Authors
Nicolás, L. ; Baró, C. ; Rodríguez, M. ; Baroja Mazo, A. ; Sole, F. ; Flores, J. M. ; Ampurdanés, C. ; Dantzer, Françoise ; Aparicio, P. ; Yélamos, J. ; Martínez Cáceres, Carlos Manuel
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Publisher
Springer Nature
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DOI
https://doi.org/10.1038/onc.2010.11
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info:eu-repo/semantics/article
Description
© 2010, Macmillan Publishers Limited. This document is the Published version of a Published Work that appeared in final form in Oncogene. To access the final edited and published work see https://doi.org/10.1038/onc.2010.11
Abstract
Poly(ADP-ribose) polymerase-2 (Parp-2) belongs to a family of enzymes that catalyse poly(ADP-ribosyl)ation of proteins. Parp-2 deficiency in mice (Parp-2−/−) results in reduced thymic cellularity associated with increased apoptosis in thymocytes, defining Parp-2 as an important mediator of T-cell survival during thymopoiesis. To determine whether there is a link between Parp-2 and the p53 DNA-damage-dependent apoptotic response, we have generated Parp-2/p53-double-null mutant mice. We found that p53−/− backgrounds completely restored the survival and development of Parp-2−/− thymocytes. However, Parp-2-deficient thymocytes accumulated high levels of DNA double-strand breaks (DSB), independently of the p53 status, in line with a function of Parp-2 as a caretaker promoting genomic stability during thymocytes development. Although Parp-2−/− mice do not have spontaneous tumours, Parp-2 deficiency accelerated spontaneous tumour development in p53-null mice, mainly T-cell lymphomas. These data suggest a synergistic interaction between Parp-2 and p53 in tumour suppression through the role of Parp-2 in DNA-damage response and genome integrity surveillance, and point to the potential importance of examining human tumours for the status of both genes.
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Citation
Oncogene, 2010, Vol. 29, pp. 2877–2883
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