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Born to Slide: Mobile Origin Licensing Factors Confer Resistance to Transcription Conflicts

88 Pages Posted: 28 Jan 2021 Publication Status: Review Complete

See all articles by Matthias Scherr

Matthias Scherr

Max Planck Institute of Biochemistry - Structure and Dynamics of Molecular Machines

Syafiq Abd Wahab

Memorial Sloan Kettering Cancer Center - Molecular Biology Program

Dirk Remus

Memorial Sloan Kettering Cancer Center - Molecular Biology Program

Karl Edward Duderstadt

Max Planck Institute of Biochemistry - Structure and Dynamics of Molecular Machines

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Abstract

Fundamental to our understanding of chromosome duplication is the idea that replication origins function both as sites where MCM helicases are loaded during the G1 phase and where synthesis begins in S phase. However, the temporal delay between these phases exposes the replisome assembly pathway to potential disruption prior to replication. Using multicolor, single-molecule imaging we systematically studied the consequences of encounters between actively transcribing RNA polymerases (RNAPs) and key replication initiation intermediates in the context of chromatin. We demonstrate that RNAP can push multiple licensed MCM helicases over long distances with individual nucleosomes overcome by ejection or displacement. Unexpectedly, we observe that MCM helicase loading intermediates can also be mobilized and repositioned by RNAP, providing a web of alternative origin specification pathways. Taken together, our observations reveal a surprising mobility in origin licensing factors that confers resistance to the complex challenges posed by diverse obstacles encountered on chromosomes.

Suggested Citation

Scherr, Matthias and Wahab, Syafiq Abd and Remus, Dirk and Duderstadt, Karl Edward, Born to Slide: Mobile Origin Licensing Factors Confer Resistance to Transcription Conflicts. Available at SSRN: https://ssrn.com/abstract=3775178 or http://dx.doi.org/10.2139/ssrn.3775178
This version of the paper has not been formally peer reviewed.

Matthias Scherr

Max Planck Institute of Biochemistry - Structure and Dynamics of Molecular Machines ( email )

Germany

Syafiq Abd Wahab

Memorial Sloan Kettering Cancer Center - Molecular Biology Program ( email )

New York, NY 10065
United States

Dirk Remus

Memorial Sloan Kettering Cancer Center - Molecular Biology Program ( email )

New York, NY 10065
United States

Karl Edward Duderstadt (Contact Author)

Max Planck Institute of Biochemistry - Structure and Dynamics of Molecular Machines ( email )

Germany

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