E1 initiator DNA binding specificity is unmasked by selective inhibition of non-specific DNA binding.
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.
Stenlund
Arne
A
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. stenlund@cshl.org
D001665:Binding Sites; D052688:Bovine papillomavirus 1 / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D018983:DNA Footprinting; D004265:DNA Helicases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; C069814:E1 protein, Bovine papillomavirus; C051550:E2 protein, Bovine papillomavirus; D014764:Viral Proteins; D004247:DNA; D004265:DNA Helicases