Mechanism and timing of Mcm2-7 ring closure during DNA replication origin licensing View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-03

AUTHORS

Simina Ticau, Larry J Friedman, Kanokwan Champasa, Ivan R Corrêa, Jeff Gelles, Stephen P Bell

ABSTRACT

The opening and closing of two ring-shaped Mcm2-7 DNA helicases is necessary to license eukaryotic origins of replication, although the mechanisms controlling these events are unclear. The origin-recognition complex (ORC), Cdc6 and Cdt1 facilitate this process by establishing a topological link between each Mcm2-7 hexamer and origin DNA. Using colocalization single-molecule spectroscopy and single-molecule Förster resonance energy transfer (FRET), we monitored ring opening and closing of Saccharomyces cerevisiae Mcm2-7 during origin licensing. The two Mcm2-7 rings were open during initial DNA association and closed sequentially, concomitant with the release of their associated Cdt1. We observed that ATP hydrolysis by Mcm2-7 was coupled to ring closure and Cdt1 release, and failure to load the first Mcm2-7 prevented recruitment of the second Mcm2-7. Our findings identify key mechanisms controlling the Mcm2-7 DNA-entry gate during origin licensing, and reveal that the two Mcm2-7 complexes are loaded via a coordinated series of events with implications for bidirectional replication initiation and quality control. More... »

PAGES

309-315

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nsmb.3375

DOI

http://dx.doi.org/10.1038/nsmb.3375

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1083801827

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28191892


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