Cell-interdependent cisplatin killing by Ku/DNA-dependent protein kinase signaling transduced through gap junctions.

ABSTRACT: Cisplatin is one of the most widely used cancer chemotherapy agents, but its mechanism of action is not fully understood. Current models suggest that cell killing by cisplatin occurs in a cell-autonomous manner by means of formation of platinum-DNA adducts that, if not removed by DNA repair, block transcription and replication. Here, we show that there is a separate cell-interdependent pathway of cisplatin killing in which damaged cells can transmit a death signal to neighboring cells. This signal is produced within the damaged cell by the kinase function of the Ku70, Ku80, and DNA-dependent protein kinase complex and is conveyed to the recipient cell by direct cell-to-cell communication through gap junctions. These findings suggest that DNA-dependent protein kinase activity and gap juncti

SUBMITTER: Jensen R 

PROVIDER: S-EPMC395935 | biostudies-literature | 2004 Apr

REPOSITORIES: biostudies-literature