Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase Journal Article


Authors: Fu, Y. V.; Yardimci, H.; Long, D. T.; Ho, V.; Guainazzi, A.; Bermudez, V. P.; Hurwitz, J.; Van Oijen, A.; Schärer, O. D.; Walter, J. C.
Article Title: Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase
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. © 2011 Elsevier Inc.
Keywords: unclassified drug; nonhuman; dna replication; dna synthesis; cell cycle protein; animals; cell cycle s phase; models, biological; protein; dna; double stranded dna; eukaryota; 5' untranslated region; chromatin immunoprecipitation; 3' untranslated region; helicase; single stranded dna; dna, single-stranded; dna binding; s phase; dna helicases; gins protein; eukaryote; xenopus; minichromosome maintenance protein 2; minichromosome maintenance protein 3; minichromosome maintenance protein 4; minichromosome maintenance protein 5; minichromosome maintenance protein 6; minichromosome maintenance protein 7; cell cycle protein 45
Journal Title: Cell
Volume: 146
Issue: 6
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2011-09-16
Start Page: 931
End Page: 941
Language: English
DOI: 10.1016/j.cell.2011.07.045
PROVIDER: scopus
PUBMED: 21925316
PMCID: PMC3209622
DOI/URL:
Notes: --- - "Export Date: 3 October 2011" - "CODEN: CELLB" - "Source: Scopus"
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  1. Jerard Hurwitz
    206 Hurwitz