1. Che-1 phosphorylation by ATM/ATR and Chk2 kinases activates p53 transcription and the G2/M checkpoint
- Author
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Bruno, Tiziana, De Nicola, Francesca, Iezzi, Simona, Lecis, Daniele, D'Angelo, Carmen, Di Padova, Monica, Corbi, Nicoletta, Dimiziani, Leopoldo, Zannini, Laura, Jekimovs, Christian, Scarsella, Marco, Porrello, Alessandro, Chersi, Alberto, Crescenzi, Marco, Leonetti, Carlo, Khanna, Kum Kum, Soddu, Silvia, Floridi, Aristide, Passananti, Claudio, and Delia, Domenico
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RNA polymerases , *PROTEINS , *GENES , *CELL proliferation , *DNA , *ANTINEOPLASTIC agents , *DNA damage - Abstract
Summary: Che-1 is a RNA polymerase II-binding protein involved in the transcription of E2F target genes and induction of cell proliferation. Here we show that Che-1 contributes to DNA damage response and that its depletion sensitizes cells to anticancer agents. The checkpoint kinases ATM/ATR and Chk2 interact with Che-1 and promote its phosphorylation and accumulation in response to DNA damage. These Che-1 modifications induce a specific recruitment of Che-1 on the TP53 and p21 promoters. Interestingly, it has a profound effect on the basal expression of p53, which is preserved following DNA damage. Notably, Che-1 contributes to the maintenance of the G2/M checkpoint induced by DNA damage. These findings identify a mechanism by which checkpoint kinases regulate responses to DNA damage. [Copyright &y& Elsevier]
- Published
- 2006
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