8zp5
From Proteopedia
Cryo-EM structure of origin recognition complex (Orc5 basic patch mutations) with ARS1 DNA bound
Structural highlights
FunctionORC5_YEAST Component of the origin recognition complex (ORC) that binds origins of replication. It has a role in both chromosomal replication and mating type transcriptional silencing. Binds to the ARS consensus sequence (ACS) of origins of replication. This subunit is a candidate for the mediation of ATP-dependent binding of ORC to origins. May also be a substrate targeting component of a cullin-RING-based E3 ubiquitin-protein ligase complex RTT101(MMS1-ORC5).[1] Publication Abstract from PubMedIn 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. DNA bending mediated by ORC is essential for replication licensing in budding yeast.,Lam WH, Yu D, Zhang Q, Lin Y, Li N, Li J, Wu Y, Zhang Y, Gao N, Tye BK, Zhai Y, Dang S Proc Natl Acad Sci U S A. 2025 Apr 8;122(14):e2502277122. doi: , 10.1073/pnas.2502277122. Epub 2025 Apr 4. PMID:40184174[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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