Loss of poly (ADP-ribose) polymerase-2 leads to rapid development of spontaneous T-cell lymphomas in p53-deficient mice

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

Publication:
Loss of poly (ADP-ribose) polymerase-2 leads to rapid development of spontaneous T-cell lymphomas in p53-deficient mice

dc.contributor.author	Nicolás, L.
dc.contributor.author	Baró, C.
dc.contributor.author	Rodríguez, M.
dc.contributor.author	Baroja Mazo, A.
dc.contributor.author	Sole, F.
dc.contributor.author	Flores, J. M.
dc.contributor.author	Ampurdanés, C.
dc.contributor.author	Dantzer, Françoise
dc.contributor.author	Aparicio, P.
dc.contributor.author	Yélamos, J.
dc.contributor.author	Martínez Cáceres, Carlos Manuel
dc.contributor.department	Anatomía y Anatomía Patológica Comparadas
dc.date.accessioned	2025-01-17T11:31:58Z
dc.date.available	2025-01-17T11:31:58Z
dc.date.issued	2010-02-15
dc.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	es
dc.description.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.	es
dc.format	application/pdf	es
dc.format.extent	7	es
dc.identifier.citation	Oncogene, 2010, Vol. 29, pp. 2877–2883
dc.identifier.doi	https://doi.org/10.1038/onc.2010.11
dc.identifier.issn	Print: 0950-9232
dc.identifier.issn	Electronic: 1476-5594
dc.identifier.uri	http://hdl.handle.net/10201/148680
dc.language	eng	es
dc.publisher	Springer Nature	es
dc.relation	This work was supported by Spanish Ministerio de Ciencia e Innovación (Grant SAF2008-01572 to JY); Generalitat de Catalunya (Grant 2009/SGR/524 to JY); Instituto de Salud Carlos III (Grant PI081150 to PA); Fundación Séneca (Grant 08643/PI/08 to PA); and funds from Centre National de la Recherche Scientifique, Association pour la Recherche contre le Cancer, Electricité de France, Comité du Haut-Rhin de la Ligue Nationale Contre le Cancer and Commissariat à l’Energie Atomique (VS, FD). LN is supported by the Spanish Ministerio de Ciencia e Innovación and AB-M is supported by Instituto de Salud Carlos III (Madrid, Spain) and the FFIS (Murcia, Spain).	es
dc.relation.publisherversion	https://www.nature.com/articles/onc201011	es
dc.rights.accessRights	info:eu-repo/semantics/restrictedAccess
dc.subject	Parp 2	es
dc.subject	P53	es
dc.subject	Tumour development	es
dc.subject	Thymocytes	es
dc.subject	V D J recombination	es
dc.subject	Double strand breaks	es
dc.title	Loss of poly (ADP-ribose) polymerase-2 leads to rapid development of spontaneous T-cell lymphomas in p53-deficient mice	es
dc.type	info:eu-repo/semantics/article	es
dspace.entity.type	Publication	es
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