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J Biol Chem, Vol. 275, Issue 5, 3522-3534, February 4, 2000
From the Cold Spring Harbor Laboratory,
Cold Spring Harbor, New York 11724
Replication of bovine papillomavirus type 1 DNA
absolutely requires the viral transcription factor E2 as well as the
initiator E1, although E1 alone has all the activities expected of an
initiator protein. E1 assembles on the DNA in a stepwise fashion and
undergoes a transition in activities from site-specific DNA-binding
protein to mobile helicase. Complex assembly is assisted by the viral transcription factor E2 at two levels. E2 acts generally as a specificity factor, which through cooperative binding with E1 generates
an initial E1 complex containing three E1 dimers bound to
ori on one face of the DNA, E1-ori.
Furthermore, E2 can promote the transition to an ori
melting complex by recruiting additional E1 molecules to
ori, effectively reducing the E1 concentration required for
ori melting. This reaction is dependent on an E2-binding site positioned distal to the precursor E1-ori complex. The
final origin melting complex has two subunits that each encircle the DNA and function independently to melt ori. The assembly
pathway we describe has implication for understanding DNA melting and unwinding reactions, which are generally poorly understood.
Transcription Factor-dependent Loading of the E1
Initiator Reveals Modular Assembly of the Papillomavirus Origin Melting
Complex*
*
This work was supported by National Institutes of Health
Grant CA 13106 (to A. S.) and in part by a Wellcome International Prize Travelling Fellowship (to C. M. S.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Cold Spring Harbor
Laboratory, P. O. Box 100, Cold Spring Harbor, New York, NY 11724. Tel.: 516-367-8407; Fax: 516-367-8454; E-mail:
Stenlund@cshl.org.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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