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dc.contributor.authorPatel, Prasanta K.
dc.contributor.authorKommajosyula, Naveen
dc.contributor.authorRosebrock, Adam
dc.contributor.authorBensimon, Aaron
dc.contributor.authorLeatherwood, Janet K.
dc.contributor.authorBechhoefer, John
dc.contributor.authorRhind, Nicholas R.
dc.date2022-08-11T08:08:51.000
dc.date.accessioned2022-08-23T16:09:52Z
dc.date.available2022-08-23T16:09:52Z
dc.date.issued2008-09-19
dc.date.submitted2009-02-19
dc.identifier.citationMol Biol Cell. 2008 Dec;19(12):5550-8. Epub 2008 Sep 17. <a href="http://dx.doi.org/10.1091/mbc.E08-06-0645">Link to article on publisher's site</a>
dc.identifier.issn1939-4586 (Electronic)
dc.identifier.doi10.1091/mbc.E08-06-0645
dc.identifier.pmid18799612
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32801
dc.description.abstractOrigins of DNA replication are generally inefficient, with most firing in fewer than half of cell cycles. However, neither the mechanism nor the importance of the regulation of origin efficiency is clear. In fission yeast, origin firing is stochastic, leading us to hypothesize that origin inefficiency and stochasticity are the result of a diffusible, rate-limiting activator. We show that the Hsk1-Dfp1 replication kinase (the fission yeast Cdc7-Dbf4 homologue) plays such a role. Increasing or decreasing Hsk1-Dfp1 levels correspondingly increases or decreases origin efficiency. Furthermore, tethering Hsk1-Dfp1 near an origin increases the efficiency of that origin, suggesting that the effective local concentration of Hsk1-Dfp1 regulates origin firing. Using photobleaching, we show that Hsk1-Dfp1 is freely diffusible in the nucleus. These results support a model in which the accessibility of replication origins to Hsk1-Dfp1 regulates origin efficiency and provides a potential mechanistic link between chromatin structure and replication timing. By manipulating Hsk1-Dfp1 levels, we show that increasing or decreasing origin firing rates leads to an increase in genomic instability, demonstrating the biological importance of appropriate origin efficiency.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=18799612&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1091/mbc.E08-06-0645
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleThe Hsk1(Cdc7) replication kinase regulates origin efficiency
dc.typeJournal Article
dc.source.journaltitleMolecular biology of the cell
dc.source.volume19
dc.source.issue12
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1354
dc.identifier.contextkey727549
html.description.abstract<p>Origins of DNA replication are generally inefficient, with most firing in fewer than half of cell cycles. However, neither the mechanism nor the importance of the regulation of origin efficiency is clear. In fission yeast, origin firing is stochastic, leading us to hypothesize that origin inefficiency and stochasticity are the result of a diffusible, rate-limiting activator. We show that the Hsk1-Dfp1 replication kinase (the fission yeast Cdc7-Dbf4 homologue) plays such a role. Increasing or decreasing Hsk1-Dfp1 levels correspondingly increases or decreases origin efficiency. Furthermore, tethering Hsk1-Dfp1 near an origin increases the efficiency of that origin, suggesting that the effective local concentration of Hsk1-Dfp1 regulates origin firing. Using photobleaching, we show that Hsk1-Dfp1 is freely diffusible in the nucleus. These results support a model in which the accessibility of replication origins to Hsk1-Dfp1 regulates origin efficiency and provides a potential mechanistic link between chromatin structure and replication timing. By manipulating Hsk1-Dfp1 levels, we show that increasing or decreasing origin firing rates leads to an increase in genomic instability, demonstrating the biological importance of appropriate origin efficiency.</p>
dc.identifier.submissionpathgsbs_sp/1354
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages5550-8


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