8ZP4

Cryo-EM structure of origin recognition complex (Orc1 to 5) with ARS1 DNA bound

Summary for 8ZP4

• Entry DOI: 10.2210/pdb8zp4/pdb
• EMDB information: 60326
• Descriptor: Origin recognition complex subunit 1, Origin recognition complex subunit 2, Origin recognition complex subunit 3, ... (9 entities in total)
• Functional Keywords: origin recognition complex, replication
• Biological source: Saccharomyces cerevisiae S288C; More
• Total number of polymer chains: 7
• Total formula weight: 413286.65

Authors

Lam, W.H.,Yu, D.,Dang, S.,Zhai, Y. (deposition date: 2024-05-29, release date: 2025-04-16)

Primary citation

Lam, W.H.,Yu, D.,Zhang, Q.,Lin, Y.,Li, N.,Li, J.,Wu, Y.,Zhang, Y.,Gao, N.,Tye, B.K.,Zhai, Y.,Dang, S.
DNA bending mediated by ORC is essential for replication licensing in budding yeast.
Proc.Natl.Acad.Sci.USA, 122:e2502277122-e2502277122, 2025

PubMed Abstract: In eukaryotes, the origin recognition complex (ORC) promotes the assembly of minichromosome maintenance 2 to 7 complexes into a head-to-head double hexamer at origin DNA in a process known as replication licensing. In this study, we present a series of cryoelectron microscopy structures of yeast ORC mutants in complex with origin DNA. We show that Orc6, the smallest subunit of ORC, utilizes its transcription factor II B-B domain to orchestrate the sequential binding of ORC to origin DNA. In addition, Orc6 plays the role of a scaffold by stabilizing the basic patch (BP) of Orc5 for ORC to capture and bend origin DNA. Importantly, disrupting DNA bending through mutating three key residues in Orc5-BP impairs ORC's ability to promote replication initiation at two points during the pre-RC assembly process. This study dissects the multifaceted role of Orc6 in orchestrating ORC's activities on DNA and underscores the vital role of DNA bending by ORC in replication licensing.

PubMed: 40184174
DOI: 10.1073/pnas.2502277122

Experimental method

ELECTRON MICROSCOPY (3.33 Å)