Kose, HB;
Larsen, NB;
Duxin, JP;
Yardimci, H;
(2019)
Dynamics of the Eukaryotic Replicative Helicase at Lagging-Strand Protein Barriers Support the Steric Exclusion Model.
Cell Reports
, 26
(8)
2113-2125.e6.
10.1016/j.celrep.2019.01.086.
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Abstract
Progression of DNA replication depends on the ability of the replisome complex to overcome nucleoprotein barriers. During eukaryotic replication, the CMG helicase translocates along the leading-strand template and unwinds the DNA double helix. While proteins bound to the leading-strand template efficiently block the helicase, the impact of lagging-strand protein obstacles on helicase translocation and replisome progression remains controversial. Here, we show that CMG and replisome progressions are impaired when proteins crosslinked to the lagging-strand template enhance the stability of duplex DNA. In contrast, proteins that exclusively interact with the lagging-strand template influence neither the translocation of isolated CMG nor replisome progression in Xenopus egg extracts. Our data imply that CMG completely excludes the lagging-strand template from the helicase central channel while unwinding DNA at the replication fork, which clarifies how two CMG helicases could freely cross one another during replication initiation and termination.
| Type: | Article |
|---|---|
| Title: | Dynamics of the Eukaryotic Replicative Helicase at Lagging-Strand Protein Barriers Support the Steric Exclusion Model |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2019.01.086 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2019.01.086 |
| Language: | English |
| Additional information: | Copyright © 2019 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org /licenses/by/4.0/). |
| Keywords: | eukaryotic DNA replication, CMG, replicative helicase, DNA-protein crosslink, single-molecule imaging, steric exclusion |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10071975 |
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