Recognition of cisplatin adducts by cellular proteins

Cisplatin is a widely used chemotherapeutic agent. It reacts with nucleophi lic bases in DNA and forms 1,2-d(ApG), 1,2-d(GpG) and 1,3-d(GpTpG) intrastr and crosslinks, interstrand crosslinks and monofunctional adducts. The pres ence of these adducts in DNA is through to be responsible for the therapeut ic efficacy of cisplatin. The exact signal transduction pathway that leads to cell cycle arrest and cell death following treatment with the drug is no t known but cell death is believed to be mediated by the recognition of the adducts by cellular proteins. Here we describe the structural information available for cisplatin and related platinum adducts, the interactions of t he adducts with cellular proteins and the implications of these interaction s for cell survival. (C) 2001 Elsevier Science B.V. All rights reserved.