MCM2-7 loading-dependent ORC release ensures genome-wide origin licensing.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 Aug 2024
24 Aug 2024
Historique:
received:
01
02
2024
accepted:
09
08
2024
medline:
26
8
2024
pubmed:
26
8
2024
entrez:
24
8
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39181881
doi: 10.1038/s41467-024-51538-9
pii: 10.1038/s41467-024-51538-9
doi:
Substances chimiques
Origin Recognition Complex
0
Saccharomyces cerevisiae Proteins
0
Minichromosome Maintenance Proteins
EC 3.6.4.12
DNA, Fungal
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7306Subventions
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/N000323/1
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/S001387/1
Organisme : RCUK | MRC | Medical Research Foundation
ID : MC_U120085811
Organisme : Wellcome Trust (Wellcome)
ID : 107903/Z/15/Z
Organisme : Wellcome Trust (Wellcome)
ID : 107903/Z/15/Z
Organisme : Wellcome Trust (Wellcome)
ID : 107903/Z/15/Z
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 336963304
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 505087959
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : RE 4094/2-1
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 101109916
Informations de copyright
© 2024. The Author(s).
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