MCM2-7 loading-dependent ORC release ensures genome-wide origin licensing
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Author(s)
Type
Journal Article
Abstract
Origin recognition complex (ORC)-dependent loading of the replicative helicase MCM2-7 onto
replication origins in G1-phase forms the basis of replication fork establishment in S-phase.
However, how ORC and MCM2-7 facilitate genome-wide DNA licensing is not fully
understood. Mapping the molecular footprints of budding yeast ORC and MCM2-7 genome-wide, we discovered that MCM2-7 loading is associated with ORC release from origins and
redistribution to non-origin sites. Our bioinformatic analysis revealed that origins are compact
units, where a single MCM2-7 double hexamer blocks repetitive loading through steric ORC
binding site occlusion. Analyses of A-elements and an improved B2-element consensus motif
uncovered that DNA shape, DNA flexibility, and the correct, face-to-face spacing of the two
DNA elements are hallmarks of ORC-binding and efficient helicase loading sites. Thus, our
work identified fundamental principles for MCM2-7 helicase loading that explain how origin
licensing is realised across the genome.
replication origins in G1-phase forms the basis of replication fork establishment in S-phase.
However, how ORC and MCM2-7 facilitate genome-wide DNA licensing is not fully
understood. Mapping the molecular footprints of budding yeast ORC and MCM2-7 genome-wide, we discovered that MCM2-7 loading is associated with ORC release from origins and
redistribution to non-origin sites. Our bioinformatic analysis revealed that origins are compact
units, where a single MCM2-7 double hexamer blocks repetitive loading through steric ORC
binding site occlusion. Analyses of A-elements and an improved B2-element consensus motif
uncovered that DNA shape, DNA flexibility, and the correct, face-to-face spacing of the two
DNA elements are hallmarks of ORC-binding and efficient helicase loading sites. Thus, our
work identified fundamental principles for MCM2-7 helicase loading that explain how origin
licensing is realised across the genome.
Date Issued
2024-08-24
Date Acceptance
2024-08-09
Citation
Nature Communications, 2024, 15
ISSN
2041-1723
Publisher
Nature Portfolio
Journal / Book Title
Nature Communications
Volume
15
Copyright Statement
© The Author(s) 2024 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.nature.com/articles/s41467-024-51538-9
Publication Status
Published
Coverage Spatial
United Kingdom
Article Number
7306
Date Publish Online
2024-08-24