DNA bending mediated by ORC is essential for replication licensing in budding yeast

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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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2025-04-04
DOI
https://doi.org/10.1073/pnas.2502277122
Citations
2
Primary Topic
DNA Repair Mechanisms
Type
article
Field-Weighted Citation Impact
1.61

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article

DNA bending mediated by ORC is essential for replication licensing in budding yeast

Ning Gao, Daqi Yu, Jian Jian Li, Yue Wu et al.
2 citations
Proceedings of the National Academy of Sciences
DNA Repair Mechanisms
1.61
article

DNA bending mediated by ORC is essential for replication licensing in budding yeast

Ning Gao, Daqi Yu, Jian Jian Li, Yue Wu, Shangyu Dang, Bik‐Kwoon Tye, Yuanliang Zhai, Yuhan Lin, Ningning Li, Yingyi Zhang, Wai Hei Lam, Qiongdan Zhang
article en
2 citations

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.

Proceedings of the National Academy of SciencesVol. 122(14)
Hong Kong University of Science and Technology (HK), Peking University (CN), Cornell University (US), King Center (US), Pediatrics and Genetics (US), Center for Life Sciences (CN), University of Hong Kong (HK)
National Natural Science Foundation of China, Research Grants Council, University Grants Committee
Openalex Percentile: Top 18%
DNA Repair Mechanisms
1.61
DOIOpen Access PDFOpenAlex
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