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dc.contributor.authorSobhy, Mohamed Abdelmaboud
dc.contributor.authorBralic, Amer
dc.contributor.authorRaducanu, Vlad-Stefan
dc.contributor.authorTakahashi, Masateru
dc.contributor.authorTehseen, Muhammad
dc.contributor.authorRashid, Fahad
dc.contributor.authorZaher, Manal
dc.contributor.authorHamdan, Samir
dc.date.accessioned2019-01-09T14:00:31Z
dc.date.available2019-01-09T14:00:31Z
dc.date.issued2018-12-22
dc.identifier.citationSobhy MA, Bralić A, Raducanu V-S, Takahashi M, Tehseen M, et al. (2018) Resolution of the Holliday junction recombination intermediate by human GEN1 at the single-molecule level. Nucleic Acids Research. Available: http://dx.doi.org/10.1093/nar/gky1280.
dc.identifier.issn0305-1048
dc.identifier.issn1362-4962
dc.identifier.doi10.1093/nar/gky1280
dc.identifier.urihttp://hdl.handle.net/10754/630771
dc.description.abstractHuman GEN1 is a cytosolic homologous recombination protein that resolves persisting four-way Holliday junctions (HJ) after the dissolution of the nuclear membrane. GEN1 dimerization has been suggested to play key role in the resolution of the HJ, but the kinetic details of its reaction remained elusive. Here, single-molecule FRET shows how human GEN1 binds the HJ and always ensures its resolution within the lifetime of the GEN1-HJ complex. GEN1 monomer generally follows the isomer bias of the HJ in its initial binding and subsequently distorts it for catalysis. GEN1 monomer remains tightly bound with no apparent dissociation until GEN1 dimer is formed and the HJ is fully resolved. Fast on- and slow off-rates of GEN1 dimer and its increased affinity to the singly-cleaved HJ enforce the forward reaction. Furthermore, GEN1 monomer binds singly-cleaved HJ tighter than intact HJ providing a fail-safe mechanism if GEN1 dimer or one of its monomers dissociates after the first cleavage. The tight binding of GEN1 monomer to intact- and singly-cleaved HJ empowers it as the last resort to process HJs that escape the primary mechanisms.
dc.description.sponsorshipACKNOWLEDGEMENTS: We thank Prof. Yuji Iwata for his help in the initial stage of cloning GEN1. We thank Yujing Ouyang for the preparation of the functionalized cover slips. We thank Dr Susan Tsutakawa, Prof. John Tainer and Dr Maged Serag for thoughtful discussions. FUNDING: King Abdullah University of Science and Technology through core funding and Competitive Research Award [CRG3 to S.M.H.]. Funding for open access charge: King Abdullah University of Science and Technology through CRG3.
dc.publisherOxford University Press (OUP)
dc.relation.urlhttps://academic.oup.com/nar/advance-article/doi/10.1093/nar/gky1280/5258024
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.titleResolution of the Holliday junction recombination intermediate by human GEN1 at the single-molecule level
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.contributor.departmentLaboratory of DNA Replication and Recombination
dc.identifier.journalNucleic Acids Research
dc.eprint.versionPublisher's Version/PDF
kaust.personSobhy, Mohamed Abdelmaboud
kaust.personBralic, Amer
kaust.personRaducanu, Vlad-Stefan
kaust.personTakahashi, Masateru
kaust.personTehseen, Muhammad
kaust.personRashid, Fahad
kaust.personZaher, Manal S.
kaust.personHamdan, Samir
refterms.dateFOA2019-01-10T08:02:08Z
dc.date.published-online2018-12-22
dc.date.published-print2019-02-28


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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Except where otherwise noted, this item's license is described as This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com