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dc.contributor.authorBadrinarayanan, Anjana
dc.contributor.authorLe, Tung
dc.contributor.authorSpille, Jan Hendrik
dc.contributor.authorCisse, Ibrahim I
dc.contributor.authorLaub, Michael T
dc.date.accessioned2018-01-19T15:42:46Z
dc.date.available2018-01-19T15:42:46Z
dc.date.issued2017-05
dc.date.submitted2016-10
dc.identifier.issn1553-7404
dc.identifier.issn1553-7390
dc.identifier.urihttp://hdl.handle.net/1721.1/113234
dc.description.abstractIn bacteria, double-strand break (DSB) repair via homologous recombination is thought to be initiated through the bi-directional degradation and resection of DNA ends by a helicase-nuclease complex such as AddAB. The activity of AddAB has been well-studied in vitro, with translocation speeds between 400–2000 bp/s on linear DNA suggesting that a large section of DNA around a break site is processed for repair. However, the translocation rate and activity of AddAB in vivo is not known, and how AddAB is regulated to prevent excessive DNA degradation around a break site is unclear. To examine the functions and mechanistic regulation of AddAB inside bacterial cells, we developed a next-generation sequencing-based approach to assay DNA processing after a site-specific DSB was introduced on the chromosome of Caulobacter crescentus. Using this assay we determined the in vivo rates of DSB processing by AddAB and found that putative chi sites attenuate processing in a RecA-dependent manner. This RecA-mediated regulation of AddAB prevents the excessive loss of DNA around a break site, limiting the effects of DSB processing on transcription. In sum, our results, taken together with prior studies, support a mechanism for regulating AddAB that couples two key events of DSB repair–the attenuation of DNA-end processing and the initiation of homology search by RecA–thereby helping to ensure that genomic integrity is maintained during DSB repair.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant 5R01GM082899)en_US
dc.description.sponsorshipHuman Frontier Science Program (Strasbourg, France) (Postdoctoral Fellowship)en_US
dc.description.sponsorshipGordon and Betty Moore Foundation (Postdoctoral Fellowship of the Life Sciences Research Foundation)en_US
dc.description.sponsorshipMassachusetts Institute of Technology (RSC Grant 2654055)en_US
dc.publisherPublic Library of Science (PLoS)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1371/JOURNAL.PGEN.1006783en_US
dc.rightsCreative Commons Attribution 4.0 International Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_US
dc.sourcePLoSen_US
dc.titleGlobal analysis of double-strand break processing reveals in vivo properties of the helicase-nuclease complex AddABen_US
dc.typeArticleen_US
dc.identifier.citationBadrinarayanan, Anjana, et al. “Global Analysis of Double-Strand Break Processing Reveals in Vivo Properties of the Helicase-Nuclease Complex AddAB.” PLOS Genetics, edited by Michael Lichten, vol. 13, no. 5, May 2017, p. e1006783.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Physicsen_US
dc.contributor.mitauthorBadrinarayanan, Anjana
dc.contributor.mitauthorLe, Tung
dc.contributor.mitauthorSpille, Jan Hendrik
dc.contributor.mitauthorCisse, Ibrahim I
dc.contributor.mitauthorLaub, Michael T
dc.relation.journalPLOS Geneticsen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2018-01-19T15:23:53Z
dspace.orderedauthorsBadrinarayanan, Anjana; Le, Tung B. K.; Spille, Jan-Hendrik; Cisse, Ibrahim I.; Laub, Michael T.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-6807-6576
dc.identifier.orcidhttps://orcid.org/0000-0003-4764-8851
dc.identifier.orcidhttps://orcid.org/0000-0001-8493-4721
dc.identifier.orcidhttps://orcid.org/0000-0002-8764-1809
dc.identifier.orcidhttps://orcid.org/0000-0002-8288-7607
mit.licensePUBLISHER_CCen_US


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