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Science 31 August 2007:
Vol. 317. no. 5842, pp. 1213 - 1216
DOI: 10.1126/science.1143664
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Reports

Structural Basis of DNA Replication Origin Recognition by an ORC Protein

Martin Gaudier, Barbara S. Schuwirth, Sarah L. Westcott, Dale B. Wigley*

DNA replication in archaea and in eukaryotes share many similarities. We report the structure of an archaeal origin recognition complex protein, ORC1, bound to an origin recognition box, a DNA sequence that is found in multiple copies at replication origins. DNA binding is mediated principally by a C-terminal winged helix domain that inserts deeply into the major and minor grooves, widening them both. However, additionalDNA contacts are made with the N-terminalAAA+ domain, which inserts into the minor groove at a characteristic G-rich sequence, inducing a 35° bend in the duplex and providing directionality to the binding site. Both contact regions also induce substantial unwinding of the DNA. The structure provides insight into the initial step in assembly of a replication origin and recruitment of minichromosome maintenance (MCM) helicase to that origin.

Cancer Research UK Clare Hall Laboratories, London Research Institute, Blanche Lane, South Mimms, Potters Bar, Herts EN6 3LD, UK.

* To whom correspondence should be addressed. E-mail: Dale.Wigley{at}cancer.org.uk

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Thermoplasma acidophilum Cdc6 protein stimulates MCM helicase activity by regulating its ATPase activity.
G. T. Haugland, N. Sakakibara, A. L. Pey, C. R. Rollor, N.-K. Birkeland, and Z. Kelman (2008)
Nucleic Acids Res. 36, 5602-5609
   Abstract »    Full Text »    PDF »
The architecture of the DNA replication origin recognition complex in Saccharomyces cerevisiae.
Z. Chen, C. Speck, P. Wendel, C. Tang, B. Stillman, and H. Li (2008)
PNAS 105, 10326-10331
   Abstract »    Full Text »    PDF »
Replication Origin Recognition and Deformation by a Heterodimeric Archaeal Orc1 Complex.
E. L. C. Dueber, J. E. Corn, S. D. Bell, and J. M. Berger (2007)
Science 317, 1210-1213
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)