E1 initiator DNA binding specificity is unmasked by selective inhibition of non-specific DNA binding

EMBO J. 2003 Feb 17;22(4):954-63. doi: 10.1093/emboj/cdg091.

Abstract

Initiator proteins are critical components of the DNA replication machinery and mark the site of initiation. This activity probably requires highly selective DNA binding; however, many initiators display modest specificity in vitro. We demonstrate that low specificity of the papillomavirus E1 initiator results from the presence of a non-specific DNA-binding activity, involved in melting, which masks the specificity intrinsic to the E1 DNA-binding domain. The viral factor E2 restores specificity through a physical interaction with E1 that suppresses non-specific binding. We propose that this arrangement, where one DNA-binding activity tethers the initiator to ori while another alters DNA structure, is a characteristic of other viral and cellular initiator proteins. This arrangement would provide an explanation for the low selectivity observed for DNA binding by initiator proteins.

Publication types

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

MeSH terms

  • Binding Sites
  • Bovine papillomavirus 1 / genetics*
  • DNA / metabolism
  • DNA Footprinting
  • DNA Helicases / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Protein Structure, Tertiary
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism

Substances

  • DNA-Binding Proteins
  • E1 protein, Bovine papillomavirus
  • E2 protein, Bovine papillomavirus
  • Viral Proteins
  • DNA
  • DNA Helicases