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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 complexprotein, ORC1, bound to an origin recognition box, a DNA sequencethat is found in multiple copies at replication origins. DNAbinding is mediated principally by a C-terminal winged helixdomain that inserts deeply into the major and minor grooves,widening them both. However, additionalDNA contacts are madewith the N-terminalAAA+ domain, which inserts into the minorgroove at a characteristic G-rich sequence, inducing a 35°bend in the duplex and providing directionality to the bindingsite. Both contact regions also induce substantial unwindingof the DNA. The structure provides insight into the initialstep in assembly of a replication origin and recruitment ofminichromosome 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
The Mcm Complex: Unwinding the Mechanism of a Replicative Helicase.
M. L. Bochman and A. Schwacha (2009)
Microbiol. Mol. Biol. Rev.
73, 652-683
|Abstract »|Full Text »|PDF »
DNA translocation activity of the multifunctional replication protein ORF904 from the archaeal plasmid pRN1.
M. Sanchez, M. Drechsler, H. Stark, and G. Lipps (2009)
Nucleic Acids Res.
37, 6831-6848
|Abstract »|Full Text »|PDF »
Functional Dissection of the Catalytic Carboxyl-Terminal Domain of Origin Recognition Complex Subunit 1 (PfORC1) of the Human Malaria Parasite Plasmodium falciparum.
A. Gupta, P. Mehra, A. Deshmukh, A. Dar, P. Mitra, N. Roy, and S. K. Dhar (2009)
Eukaryot. Cell
8, 1341-1351
|Abstract »|Full Text »|PDF »
Archaeal eukaryote-like Orc1/Cdc6 initiators physically interact with DNA polymerase B1 and regulate its functions.
L. Zhang, L. Zhang, Y. Liu, S. Yang, C. Gao, H. Gong, Y. Feng, and Z.-G. He (2009)
PNAS
106, 7792-7797
|Abstract »|Full Text »|PDF »
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 »