Recognition of cisplatin adducts by cellular proteins

Mutat Res. 2001 Jul 1;478(1-2):1-21. doi: 10.1016/s0027-5107(01)00142-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antigens, Nuclear*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cisplatin / chemistry
  • Cisplatin / pharmacology*
  • DNA Adducts / chemistry
  • DNA Adducts / drug effects*
  • DNA Adducts / metabolism
  • DNA Helicases*
  • DNA Repair
  • DNA-Binding Proteins / metabolism
  • Deoxyribodipyrimidine Photo-Lyase / metabolism
  • High Mobility Group Proteins / metabolism
  • Humans
  • Ku Autoantigen
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Proteins / metabolism*

Substances

  • Antigens, Nuclear
  • Antineoplastic Agents
  • DNA Adducts
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Nuclear Proteins
  • Proteins
  • DNA Helicases
  • XRCC5 protein, human
  • Xrcc6 protein, human
  • Deoxyribodipyrimidine Photo-Lyase
  • Ku Autoantigen
  • Cisplatin