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dc.contributor.authorKlein, Kyle
dc.contributor.authorWang, Weitao
dc.contributor.authorBorrman, Tyler M.
dc.contributor.authorChan, Saki
dc.contributor.authorZhang, Denghong
dc.contributor.authorWeng, Zhiping
dc.contributor.authorHastie, Alex
dc.contributor.authorChen, Chunlong
dc.contributor.authorGilbert, David M.
dc.contributor.authorRhind, Nicholas R.
dc.date2022-08-11T08:08:23.000
dc.date.accessioned2022-08-23T15:53:12Z
dc.date.available2022-08-23T15:53:12Z
dc.date.issued2017-11-06
dc.date.submitted2018-06-11
dc.identifier.citation<p>bioRxiv 214841; doi: https://doi.org/10.1101/214841. <a href="https://doi.org/10.1101/214841" target="_blank">Link to preprint on bioRxiv service. </a></p>
dc.identifier.doi10.1101/214841
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29306
dc.description.abstractThe timing of DNA replication is largely regulated by the location and timing of replication origin firing. Therefore, much effort has been invested in identifying and analyzing human replication origins. However, the heterogeneous nature of eukaryotic replication kinetics and the low efficiency of individual origins in metazoans has made mapping the location and timing of replication initiation in human cells difficult. We have mapped early-firing origins in HeLa cells using Optical Replication Mapping, a high-throughput single-molecule approach based on Bionano Genomics genomic mapping technology. The single-molecule nature and 290-fold coverage of our dataset allowed us to identify origins that fire with as little as 1% efficiency. We find sites of human replication initiation in early S phase are not confined to well-defined efficient replication origins, but are instead distributed across broad initiation zones consisting of many inefficient origins. These early-firing initiation zones co-localize with initiation zones inferred from Okazaki-fragment-mapping analysis and are enriched in ORC1 binding sites. Although most early-firing origins fire in early-replication regions of the genome, a significant number fire in late-replicating regions, suggesting that the major difference between origins in early and late replicating regions is their probability of firing in early S-phase, as opposed to qualitative differences in their firing-time distributions. This observation is consistent with stochastic models of origin timing regulation, which explain the regulation of replication timing in yeast.
dc.language.isoen_US
dc.rightsThe copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC 4.0 International license.
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectgenomics
dc.subjectDNA replication
dc.subjectOptical Replication Mapping
dc.subjectBionano Genomics genomic mapping technology
dc.subjectBiochemistry
dc.subjectCells
dc.subjectComputational Biology
dc.subjectGenetic Phenomena
dc.subjectGenomics
dc.subjectInvestigative Techniques
dc.titleGenome-Wide Identification of Early-Firing Human Replication Origins by Optical Replication Mapping [preprint]
dc.typePreprint
dc.source.journaltitlebioRxiv
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2537&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1532
dc.identifier.contextkey12290845
refterms.dateFOA2022-08-23T15:53:12Z
html.description.abstract<p>The timing of DNA replication is largely regulated by the location and timing of replication origin firing. Therefore, much effort has been invested in identifying and analyzing human replication origins. However, the heterogeneous nature of eukaryotic replication kinetics and the low efficiency of individual origins in metazoans has made mapping the location and timing of replication initiation in human cells difficult. We have mapped early-firing origins in HeLa cells using Optical Replication Mapping, a high-throughput single-molecule approach based on Bionano Genomics genomic mapping technology. The single-molecule nature and 290-fold coverage of our dataset allowed us to identify origins that fire with as little as 1% efficiency. We find sites of human replication initiation in early S phase are not confined to well-defined efficient replication origins, but are instead distributed across broad initiation zones consisting of many inefficient origins. These early-firing initiation zones co-localize with initiation zones inferred from Okazaki-fragment-mapping analysis and are enriched in ORC1 binding sites. Although most early-firing origins fire in early-replication regions of the genome, a significant number fire in late-replicating regions, suggesting that the major difference between origins in early and late replicating regions is their probability of firing in early S-phase, as opposed to qualitative differences in their firing-time distributions. This observation is consistent with stochastic models of origin timing regulation, which explain the regulation of replication timing in yeast.</p>
dc.identifier.submissionpathfaculty_pubs/1532
dc.contributor.departmentProgram in Bioinformatics and Integrative Biology
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology


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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC 4.0 International license.
Except where otherwise noted, this item's license is described as The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC 4.0 International license.