Author/Authors :
Bruno، نويسنده , , Tiziana and De Nicola، نويسنده , , Francesca and Iezzi، نويسنده , , Simona and Lecis، نويسنده , , Daniele and DʹAngelo، نويسنده , , Carmen and Di Padova، نويسنده , , Monica and Corbi، نويسنده , , Nicoletta and Dimiziani، نويسنده , , Leopoldo and Zannini، نويسنده , , Laura and Jekimovs، نويسنده , , Christian and Scarsella، نويسنده , , Marco and Porrello، نويسنده , , Alessandro and Chersi، نويسنده , , Alberto and Crescenzi، نويسنده , , Marco and Leonetti، نويسنده , , Carlo and Khanna، نويسنده , , Kum Kum and Soddu، نويسنده , , Silvia and Floridi، نويسنده , , Aristide and Passananti، نويسنده , , Claudio and Delia، نويسنده , , Domenico and Fanciulli، نويسنده , , Maurizio، نويسنده ,
Abstract :
Summary
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.
