Evidence that O6-alkylguanine-DNA alkyltransferase becomes covalently bound to DNA containing 1,3-bis(2-chloroethyl)-1-nitrosourea-induced precursors of interstrand cross-links

Biochem Biophys Res Commun. 1987 Jan 30;142(2):341-7. doi: 10.1016/0006-291x(87)90279-8.

Abstract

The reaction of partially purified human O6-alkylguanine-DNA alkyltransferase with 1,3-bis(2-chloroethyl)-1-nitrosourea-treated DNA resulted in formation of a DNA-protein covalent complex. Complex formation required active alkyltransferase and brief treatment of DNA with the drug. DNA lost its capacity to form the complex once drug-induced DNA interstrand cross-links were completely formed. These results are consistent with a model in which the transferase catalyzes cleavage at O6-guanine and transfer of the alkyl moiety in a putative O6, N1-ethanoguanine intermediate of cross-link formation. DNA-protein complex formation presumably results when the transferase accepts the N1-ethanoguanine-DNA structure, analogous to its acceptance of simple alkyl groups.

Publication types

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

MeSH terms

  • Carmustine / pharmacology*
  • Cross-Linking Reagents / pharmacology*
  • DNA / metabolism*
  • Methyltransferases / metabolism*
  • O(6)-Methylguanine-DNA Methyltransferase

Substances

  • Cross-Linking Reagents
  • DNA
  • Methyltransferases
  • O(6)-Methylguanine-DNA Methyltransferase
  • Carmustine