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Nucleoporins facilitate ORC loading onto chromatin

Authors :
Logan Richards
Christopher L. Lord
Mary Lauren Benton
John A. Capra
Jared T. Nordman
Source :
Cell Reports. 41:111590
Publication Year :
2022
Publisher :
Elsevier BV, 2022.

Abstract

SUMMARYThe origin recognition complex (ORC) binds throughout the genome to initiate DNA replication. In metazoans, it is still unclear how ORC is targeted to specific loci to facilitate helicase loading and replication initiation. Here, we performed immunoprecipitations coupled with mass spectrometry for ORC2 in Drosophila embryos. Surprisingly, we found that ORC2 associates with multiple subunits of the Nup107-160 subcomplex of the nuclear pore. Bioinformatic analysis revealed that, relative to all modENCODE factors, nucleoporins are among the most enriched factors at ORC2 binding sites. Critically, depletion of the nucleoporin Elys, a member of the Nup107-160 complex, results in decreased ORC2 loading onto chromatin. Depleting Elys also sensitized cells to replication fork stalling, which could reflect a defect in establishing dormant replication origins. Our work reveals a new connection between ORC, replication initiation and nucleoporins, highlighting a previously unrecognized function of nucleoporins in metazoan replication initiation.

Details

ISSN :
22111247
Volume :
41
Database :
OpenAIRE
Journal :
Cell Reports
Accession number :
edsair.doi.dedup.....45a9ed28bbf09a1a9f4c1ec08bf3d33b