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Updated: Sep 29, 2025

Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
Published on: April 29, 2010
Mobile origin-licensing factors confer resistance to conflicts with RNA polymerase
Matthias J Scherr1, Syafiq Abd Wahab2, Dirk Remus2
1Structure and Dynamics of Molecular Machines, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Active RNA polymerases can displace MCM helicases during chromosome duplication. Unexpectedly, these displaced helicase loading intermediates can continue origin licensing, revealing flexible pathways for replication initiation.
Area of Science:
- Molecular Biology
- Chromatin Dynamics
- DNA Replication
Background:
- Chromosome duplication relies on MCM helicase loading in G1 and initiation in S phase.
- Temporal gaps between cell cycle phases risk replisome assembly disruption.
- Understanding conflicts between transcription and replication is crucial.
Purpose of the Study:
- To investigate the impact of RNA polymerase (RNAP) encounters on replication initiation intermediates.
- To analyze the mobility and licensing capacity of MCM helicases when interacting with RNAP.
- To uncover alternative origin specification pathways.
Main Methods:
- Utilized multicolor, single-molecule imaging techniques.
- Systematically studied interactions between transcribing RNAPs and replication initiation intermediates in chromatin.
- Observed dynamic behavior of MCM helicases and nucleosomes during these encounters.
Main Results:
- RNAP actively displaces multiple licensed MCM helicases over long distances, ejecting nucleosomes.
- MCM helicase loading intermediates can be repositioned by RNAP and subsequently resume origin licensing.
- Identified alternative origin specification pathways facilitated by RNAP-mediated repositioning.
Conclusions:
- Origin-licensing factors exhibit significant mobility, enhancing chromosome duplication resilience.
- RNAP-replication initiation interactions reveal complex, adaptable mechanisms for origin specification.
- These findings challenge static models of replication origin function.
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