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Depositordc.contributorTaylor, Martin
Funderdc.contributor.otherMRC - Medical Research Councilen_UK
Data Creatordc.creatorTaylor, Martin
Data Creatordc.creatorKemp, Harriet
Data Creatordc.creatorMarion de Procé, Sophie
Data Creatordc.creatorReijns, Martin
Data Creatordc.creatorDing, James
Data Creatordc.creatorJackson, Andrew
Date Accessioneddc.date.accessioned2015-01-23T13:45:33Z
Date Availabledc.date.available2015-01-26T13:45:33Z
Citationdc.identifier.citationTaylor, Martin; Kemp, Harriet; Marion de Procé, Sophie; Reijns, Martin; Ding, James; Jackson, Andrew. (2015). Lagging strand replication shapes the mutational landscape of the genome, [dataset]. University of Edinburgh. MRC Institute of Genetics and Molecular Medicine. MRC Human Genetics Unit. http://dx.doi.org/10.7488/ds/204.en
Persistent Identifierdc.identifier.urihttp://hdl.handle.net/10283/701
Persistent Identifierdc.identifier.urihttp://dx.doi.org/10.7488/ds/204
Dataset Description (abstract)dc.description.abstractThe origin of mutations is central to understanding evolution and of key relevance to health. Variation occurs non-randomly across the genome, and mechanisms for this remain to be defined. Here we report that the 5' ends of Okazaki fragments have significantly increased levels of nucleotide substitution, indicating a replicative origin for such mutations. Using a novel method, emRiboSeq, we map the genome-wide contribution of polymerases, and show that despite Okazaki fragment processing, DNA synthesized by error-prone polymerase-alpha (Pol-alpha) is retained in vivo, comprising ~1.5% of the mature genome. We propose that DNA-binding proteins that rapidly re-associate post-replication act as partial barriers to Pol-delta-mediated displacement of Pol-alpha-synthesized DNA, resulting in incorporation of such Pol-alpha tracts and increased mutation rates at specific sites. We observe a mutational cost to chromatin and regulatory protein binding, resulting in mutation hotspots at regulatory elements, with signatures of this process detectable in both yeast and humans.en_UK
Dataset Description (TOC)dc.description.tableofcontentsSee dataShareREADME.txten_UK
Languagedc.language.isoengen_UK
Publisherdc.publisherUniversity of Edinburgh. MRC Institute of Genetics and Molecular Medicine. MRC Human Genetics Uniten_UK
Relation (Is Referenced By)dc.relation.isreferencedbyhttp://dx.doi.org/10.1038/nature14183en_UK
Relation (Is Referenced By)dc.relation.isreferencedbyhttps://github.com/taylorLab/LaggingStrand
Relation (Is Referenced By)dc.relation.isreferencedbyReijns, MAM, Kemp, H, Ding, J, Marion de Procé, S, Jackson, P, Taylor, M. (2015) "Lagging-strand replication shapes the mutational landscape of the genome" Nature, http://dx.doi.org/10.1038/nature14183 .
Sourcedc.sourcehttp://www.sciencemag.org/site/feature/data/raghu1064351/SmoothedPooledHLData/smoothedpooledHLdata.htmlen_UK
Sourcedc.sourcehttp://hgdownload.soe.ucsc.edu/goldenPath/sacCer3/multiz7way/maf/en_UK
Sourcedc.sourceftp://ftp.sanger.ac.uk/pub/users/dmc/yeast/latest/misc.tgzen_UK
Subjectdc.subjectDNAen_UK
Subjectdc.subjectmutationen_UK
Subjectdc.subjectreplicationen_UK
Subjectdc.subjectlagging stranden_UK
Subject Classificationdc.subject.classificationBiological Sciences::Molecular Biology Biophysics and Biochemistryen_UK
Titledc.titleLagging strand replication shapes the mutational landscape of the genomeen_UK
Typedc.typedataseten_UK

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