22P Emerging role of histone acetyltransferase CBP in breast cancer cells undergoing DNA damage

DNA damage response and repair defects resulted from genetic epigenetic alterations are frequently observed among breast cancer patients eventually affect their to chemo- radiotherapies. Among the alterations, histone acetyltransferase CREB-binding protein (CBP) was found be dysregulated in cells. Despite of many reports that demonstrated role CBP repair, involvement initial events activating pathways potential targeting therapy remains poorly understood. Here we set out explore normal Cancer cell lines were used examine expression, stability, activity its interaction with other proteins after induction by chemotherapeutic agent or radiation. In addition, immunofluorescence, western blot, comet assay, colony formation assay proximity ligation performed inhibition downregulation under damage. Our results showed is stabilized recruited at sites double strand breaks. The depletion impaired capacity subsequently increased sensitivity cells radiotherapy, without influencing behavior Mechanistically, form a stable complex ATM, central regulator response, treatment damaging agent. Furthermore, autophosphorylation ATM cells, suggesting it’s pivotal activation. impact on ATM's kinase further augmented reduction phosphorylation downstream including Chk2, Chk1 p53 CBP-depleted Interestingly, did not interfere activation non-cancerous data highlights functional damage, particularly suggest could useful target modulate cellular agents cancer.