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Science 31 August 2007:
Vol. 317. no. 5842, pp. 1210 - 1213
DOI: 10.1126/science.1143690
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Reports

Replication Origin Recognition and Deformation by a Heterodimeric Archaeal Orc1 Complex

Erin L. Cunningham Dueber,1,2 Jacob E. Corn,2 Stephen D. Bell,3 James M. Berger2*

The faithful duplication of genetic material depends on essential DNA replication initiation factors. Cellular initiators form higher-order assemblies on replication origins, using adenosine triphosphate (ATP) to locally remodel duplex DNA and facilitate proper loading of synthetic replisomal components. To better understand initiator function, we determined the 3.4 angstrom–resolution structure of an archaeal Cdc6/Orc1 heterodimer bound to origin DNA. The structure demonstrates that, in addition to conventional DNA binding elements, initiators use their AAA+ ATPase domains to recognize origin DNA. Together these interactions establish the polarity of initiator assembly on the origin and induce substantial distortions into origin DNA strands. Biochemical and comparative analyses indicate that AAA+/DNA contacts observed in the structure are dynamic and evolutionarily conserved, suggesting that the complex forms a core component of the basal initiation machinery.

1 Miller Institute for Basic Research in Science, 2536 Channing Way 5190, University of California, Berkeley, CA 94720, USA.
2 Department of Molecular and Cell Biology, QB3 Institute, Stanley Hall 3220, University of California, Berkeley, CA 94720, USA.
3 Medical Research Council (MRC) Cancer Cell Unit, Hutchison MRC Research Centre, Hills Road, Cambridge CB2 2XZ, UK.

* To whom correspondence should be addressed. E-mail: jmberger{at}berkeley.edu

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