Show simple item record

dc.contributor.authorDuzdevich, Daniel
dc.contributor.authorTicau, Simina
dc.contributor.authorGreene, Eric C.
dc.contributor.authorWarner, Megan Dobbins
dc.contributor.authorIvica, Nikola
dc.contributor.authorBell, Stephen P
dc.date.accessioned2017-01-05T19:24:21Z
dc.date.available2017-01-05T19:24:21Z
dc.date.issued2015-05
dc.identifier.issn10972765
dc.identifier.urihttp://hdl.handle.net/1721.1/106210
dc.description.abstractEukaryotic replication initiation is highly regulated and dynamic. It begins with the origin recognition complex (ORC) binding DNA sites called origins of replication. ORC, together with Cdc6 and Cdt1, mediate pre-replicative complex (pre-RC) assembly by loading a double hexamer of Mcm2–7: the core of the replicative helicase. Here, we use single-molecule imaging to directly visualize Saccharomyces cerevisiae pre-RC assembly and replisome firing in real time. We show that ORC can locate and stably bind origins within large tracts of non-origin DNA and that Cdc6 drives ordered pre-RC assembly. We further show that the dynamics of the ORC-Cdc6 interaction dictate Mcm2–7 loading specificity and that Mcm2–7 double hexamers form preferentially at a native origin sequence. Finally, we demonstrate that single Mcm2–7 hexamers propagate bidirectionally, monotonically, and processively as constituents of active replisomes.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant GM52339)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Pre-Doctoral Training Grant GM007287)en_US
dc.description.sponsorshipNational Science Foundation (U.S.) (Graduate Research Fellowship 1122374)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.molcel.2015.03.017en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleThe Dynamics of Eukaryotic Replication Initiation: Origin Specificity, Licensing, and Firing at the Single-Molecule Levelen_US
dc.typeArticleen_US
dc.identifier.citationDuzdevich, Daniel et al. “The Dynamics of Eukaryotic Replication Initiation: Origin Specificity, Licensing, and Firing at the Single-Molecule Level.” Molecular Cell 58.3 (2015): 483–494.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorWarner, Megan Dobbins
dc.contributor.mitauthorIvica, Nikola
dc.contributor.mitauthorBell, Stephen P
dc.relation.journalMolecular Cellen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsDuzdevich, Daniel; Warner, Megan D.; Ticau, Simina; Ivica, Nikola A.; Bell, Stephen P.; Greene, Eric C.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0003-1736-6343
dc.identifier.orcidhttps://orcid.org/0000-0002-0124-0087
dc.identifier.orcidhttps://orcid.org/0000-0002-2876-610X
mit.licensePUBLISHER_CCen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record