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Nucleoporins facilitate ORC loading onto chromatin.
Logan Richards1, Christopher L Lord1, Mary Lauren Benton2
1Department of Biological Sciences, Vanderbilt University, Nashville, TN 37232, USA.
Cell Reports
|November 9, 2022
Summary
The origin recognition complex (ORC) interacts with nuclear pore proteins in fruit flies, revealing a novel role for these structures in initiating DNA replication. This finding suggests nucleoporins help target ORC to specific genomic sites.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The origin recognition complex (ORC) is essential for initiating DNA replication genome-wide.
- Mechanisms for targeting ORC to specific DNA replication origins in metazoans remain poorly understood.
Purpose of the Study:
- To investigate the molecular interactions and genomic targeting of ORC in metazoan DNA replication.
- To identify novel factors involved in regulating ORC function and replication initiation.
Main Methods:
- Immunoprecipitation coupled with mass spectrometry (IP-MS) was used to identify ORC2 interacting proteins in Drosophila embryos.
- Bioinformatic analysis was performed to assess the enrichment of factors at ORC2 binding sites.
- Depletion of specific nucleoporins (Elys) was conducted to evaluate their role in ORC loading and replication.
Main Results:
- ORC2 was found to associate with multiple subunits of the Nup107-160 nuclear pore subcomplex.
- Nucleoporins were significantly enriched at ORC2 binding sites compared to other genomic factors.
- Depletion of the nucleoporin Elys reduced ORC2 chromatin loading and increased replication fork stalling.
Conclusions:
- This study establishes a novel link between the origin recognition complex (ORC) and nuclear pore proteins (nucleoporins).
- Nucleoporins, specifically the Nup107-160 complex, are implicated in regulating ORC targeting to chromatin.
- These findings suggest a previously unrecognized function for nucleoporins in facilitating metazoan DNA replication initiation.
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