Recognition of cisplatin adducts by cellular proteins.
Cisplatin is a widely used chemotherapeutic agent. It reacts with nucleophilic bases in DNA and forms 1,2-d(ApG), 1,2-d(GpG) and 1,3-d(GpTpG) intrastrand crosslinks, interstrand crosslinks and monofunctional adducts. The presence of these adducts in DNA is through to be responsible for the therapeutic efficacy of cisplatin. The exact signal transduction pathway that leads to cell cycle arrest and cell death following treatment with the drug is not 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 the adducts with cellular proteins and the implications of these interactions for cell survival.
Kartalou
M
M
Department of Chemistry, Division of Bioengineering and Environmental Health, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Essigmann
J M
JM
D000818:Animals; D034961:Antigens, Nuclear; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology*; D018736:DNA Adducts / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D004265:DNA Helicases; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000378:metabolism; D006801:Humans; D000072200:Ku Autoantigen; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*
D034961:Antigens, Nuclear; D000970:Antineoplastic Agents; D018736:DNA Adducts; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; D011506:Proteins; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D004255:Deoxyribodipyrimidine Photo-Lyase; D000072200:Ku Autoantigen; D002945:Cisplatin