CDC6 association with the ORC:origin complex / Cul8-RING ubiquitin ligase complex / maintenance of rDNA / Assembly of the ORC complex at the origin of replication / nuclear origin of replication recognition complex / pre-replicative complex assembly involved in nuclear cell cycle DNA replication / Activation of the pre-replicative complex / nucleosome organization / nuclear pre-replicative complex / Activation of ATR in response to replication stress ...CDC6 association with the ORC:origin complex / Cul8-RING ubiquitin ligase complex / maintenance of rDNA / Assembly of the ORC complex at the origin of replication / nuclear origin of replication recognition complex / pre-replicative complex assembly involved in nuclear cell cycle DNA replication / Activation of the pre-replicative complex / nucleosome organization / nuclear pre-replicative complex / Activation of ATR in response to replication stress / DNA replication preinitiation complex / mitotic DNA replication checkpoint signaling / silent mating-type cassette heterochromatin formation / Orc1 removal from chromatin / regulation of DNA replication / DNA replication origin binding / DNA replication initiation / subtelomeric heterochromatin formation / nucleosome binding / chromosome, telomeric region / chromatin binding / ATP hydrolysis activity / nucleoplasm / ATP binding / nucleus / metal ion binding Similarity search - Function
Journal: Proc Natl Acad Sci U S A / Year: 2025 Title: DNA bending mediated by ORC is essential for replication licensing in budding yeast. Authors: Wai Hei Lam / Daqi Yu / Qiongdan Zhang / Yuhan Lin / Ningning Li / Jian Li / Yue Wu / Yingyi Zhang / Ning Gao / Bik Kwoon Tye / Yuanliang Zhai / Shangyu Dang / 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 ...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.
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