Shaping up for a new start

Alderton, Gemma K.

doi:10.1038/nrm2274

Research Highlight
Published: October 2007

DNA replication

Shaping up for a new start

Gemma K. Alderton

Nature Reviews Molecular Cell Biology volume 8, page 754 (2007)Cite this article

268 Accesses
Metrics details

Access through your institution

Buy or subscribe

Using multiwavelength anomalous dispersion, James Berger and colleagues solved the structure of the co-crystallized initiator proteins Orc1-1 and Orc1-3 from Sulfolobus solfataricus on a 33-bp fragment of DNA encompassing their binding sites. Orc1-1 and Orc1-3 form a large, positively charged surface that requires WHD–DNA and, surprisingly, AAA⁺–DNA contacts. Both the helix-turn-helix (HTH) and β-hairpin wing motifs that comprise the WHD bind over a full turn of DNA, which forms a larger WHD–DNA interface than conventional modes. Furthermore, mutations in the HTH or β-hairpin wing motifs reduced the affinities of Orc1-1 and Orc1-3 for their binding sites, and binding was completely abolished by simultaneous mutation of the HTH and β-hairpin wing motifs.

In a separate study, Dale Wigley and colleagues determined the crystal structure of Orc1, an initiator protein in Aeropyrum pernix, bound to a 22-bp fragment of DNA containing its specific target site, ori1. The WHD of Orc1 bound DNA in a canonical manner and led to widening of the helix, which further facilitated the Orc1–DNA contacts. They also showed that the AAA⁺ domain of Orc1 made substantial contact with the DNA; the contacts observed in the crystal structures were consistent with DNA footprint experiments. Moreover, using isothermal calorimetry, they showed that a single WHD bound a single origin recognition box (ORB; two pairs of which surround the replication start site within ori1).

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

Purchase on SpringerLink
Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

ORIGINAL RESEARCH PAPERS

Cunningham Dueber, E. L. et al. Replication origin recognition and deformation by a heterodimeric archaeal Orc1 complex. Science 317, 1210–1213 (2007)
Article Google Scholar
Gaudier, M. et al. Structural basis of DNA replication origin recognition by an ORC protein. Science 317, 1213–1216 (2007)
Article CAS PubMed Google Scholar