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Selective Bypass of a Lagging Strand Roadblock by the Eukaryotic Replicative DNA Helicase

Fu, Yu V; Yardimci, Hasan; Long, David T; The, Vinh Ho; Guainazzi, Angelo; Bermudez, Vladimir P; Hurwitz, Jerard; ... Walter, Johannes C; + view all (2011) Selective Bypass of a Lagging Strand Roadblock by the Eukaryotic Replicative DNA Helicase. CELL , 146 (6) pp. 931-941. 10.1016/j.cell.2011.07.045. Green open access

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Abstract

The eukaryotic replicative DNA helicase, CMG, unwinds DNA by an unknown mechanism. In some models, CMG encircles and translocates along one strand of DNA while excluding the other strand. In others, CMG encircles and translocates along duplex DNA. To distinguish between these models, replisomes were confronted with strand-specific DNA roadblocks in Xenopus egg extracts. An ssDNA translocase should stall at an obstruction on the translocation strand but not the excluded strand, whereas a dsDNA translocase should stall at obstructions on either strand. We found that replisomes bypass large roadblocks on the lagging strand template much more readily than on the leading strand template. Our results indicate that CMG is a 3′ to 5′ ssDNA translocase, consistent with unwinding via “steric exclusion.” Given that MCM2-7 encircles dsDNA in G1, the data imply that formation of CMG in S phase involves remodeling of MCM2-7 from a dsDNA to a ssDNA binding mode.

Type: Article
Title: Selective Bypass of a Lagging Strand Roadblock by the Eukaryotic Replicative DNA Helicase
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2011.07.045
Publisher version: https://doi.org/10.1016/j.cell.2011.07.045
Language: English
Additional information: Articles published under an Elsevier user license are protected by copyright and may be used for non-commercial purposes. Users may access, download, copy, translate, text mine and data mine the articles. https://www.elsevier.com/about/policies-and-standards/open-access-licenses/elsevier-user
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/10191057
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