Poly(ADP-ribose) polymerase 1 (PARP-1) catalyzes a post-translational modification that plays a crucial role in coordinating the signalling cascade in response to stress stimuli. During the DNA damage response, phosphorylation by ataxia telangiectasia mutated (ATM) kinase and checkpoint kinase Chk2 induces the stabilization of Che-1 protein, which is critical for the maintenance of G2/M arrest. In this study we showed that poly(ADP-ribosyl)ation, beyond phosphorylation, is involved in the regulation of Che-1 stabilization following DNA damage. We demonstrated that Che-1 accumulation upon doxorubicin treatment is reduced after the inhibition of PARP activity in HCT116 cells and in PARP-1 knock-out or silenced cells. In accordance, impairment in Che-1 accumulation by PARP inhibition reduced Che-1 occupancy at p21 promoter and affected the expression of the corresponding gene. Epistasis experiments showed that the effect of poly(ADP-ribosyl)ation on Che-1 stabilization is independent from ATM kinase activity. Indeed we demonstrated that Che-1 protein co-immunoprecipitates with ADP-ribose polymers and that PARP-1 directly interacts with Che-1, promoting its modification in vitro and in vivo. (C) 2011 Elsevier B.V. All rights reserved.

Poly(ADP-ribosyl)ation affects stabilization of Che-1 protein in response to DNA damage / Bacalini, MARIA GIULIA; Debora Di, Lonardo; Catizone, Angiolina; Ciccarone, Fabio; Tiziana, Bruno; Zampieri, Michele; Guastafierro, Tiziana; Calabrese, Roberta; Maurizio, Fanciulli; Claudio, Passananti; Caiafa, Paola; Reale, Anna. - In: DNA REPAIR. - ISSN 1568-7864. - STAMPA. - 10:4(2011), pp. 380-389. [10.1016/j.dnarep.2011.01.002]

Poly(ADP-ribosyl)ation affects stabilization of Che-1 protein in response to DNA damage

BACALINI, MARIA GIULIA;CATIZONE, Angiolina;CICCARONE, FABIO;ZAMPIERI, Michele;GUASTAFIERRO, Tiziana;CALABRESE, ROBERTA;CAIAFA, Paola;REALE, Anna
2011

Abstract

Poly(ADP-ribose) polymerase 1 (PARP-1) catalyzes a post-translational modification that plays a crucial role in coordinating the signalling cascade in response to stress stimuli. During the DNA damage response, phosphorylation by ataxia telangiectasia mutated (ATM) kinase and checkpoint kinase Chk2 induces the stabilization of Che-1 protein, which is critical for the maintenance of G2/M arrest. In this study we showed that poly(ADP-ribosyl)ation, beyond phosphorylation, is involved in the regulation of Che-1 stabilization following DNA damage. We demonstrated that Che-1 accumulation upon doxorubicin treatment is reduced after the inhibition of PARP activity in HCT116 cells and in PARP-1 knock-out or silenced cells. In accordance, impairment in Che-1 accumulation by PARP inhibition reduced Che-1 occupancy at p21 promoter and affected the expression of the corresponding gene. Epistasis experiments showed that the effect of poly(ADP-ribosyl)ation on Che-1 stabilization is independent from ATM kinase activity. Indeed we demonstrated that Che-1 protein co-immunoprecipitates with ADP-ribose polymers and that PARP-1 directly interacts with Che-1, promoting its modification in vitro and in vivo. (C) 2011 Elsevier B.V. All rights reserved.
2011
che-1; dna damage response; parp inhibitor; parp-1; post-translational modification
01 Pubblicazione su rivista::01a Articolo in rivista
Poly(ADP-ribosyl)ation affects stabilization of Che-1 protein in response to DNA damage / Bacalini, MARIA GIULIA; Debora Di, Lonardo; Catizone, Angiolina; Ciccarone, Fabio; Tiziana, Bruno; Zampieri, Michele; Guastafierro, Tiziana; Calabrese, Roberta; Maurizio, Fanciulli; Claudio, Passananti; Caiafa, Paola; Reale, Anna. - In: DNA REPAIR. - ISSN 1568-7864. - STAMPA. - 10:4(2011), pp. 380-389. [10.1016/j.dnarep.2011.01.002]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/387438
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