{"data":{"id":"10.6084/m9.figshare.1451388","type":"dois","attributes":{"doi":"10.6084/m9.figshare.1451388","prefix":"10.6084","suffix":"m9.figshare.1451388","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Bologna, Serena","nameType":"Personal","givenName":"Serena","familyName":"Bologna","affiliation":[],"nameIdentifiers":[]},{"name":"Altmannova, Veronika","nameType":"Personal","givenName":"Veronika","familyName":"Altmannova","affiliation":[],"nameIdentifiers":[]},{"name":"Valtorta, Emanuele","nameType":"Personal","givenName":"Emanuele","familyName":"Valtorta","affiliation":[],"nameIdentifiers":[]},{"name":"Koenig, Christiane","nameType":"Personal","givenName":"Christiane","familyName":"Koenig","affiliation":[],"nameIdentifiers":[]},{"name":"Liberali, Prisca","nameType":"Personal","givenName":"Prisca","familyName":"Liberali","affiliation":[],"nameIdentifiers":[]},{"name":"Gentili, Christian","nameType":"Personal","givenName":"Christian","familyName":"Gentili","affiliation":[],"nameIdentifiers":[]},{"name":"Anrather, Dorothea","nameType":"Personal","givenName":"Dorothea","familyName":"Anrather","affiliation":[],"nameIdentifiers":[]},{"name":"Ammerer, Gustav","nameType":"Personal","givenName":"Gustav","familyName":"Ammerer","affiliation":[],"nameIdentifiers":[]},{"name":"Pelkmans, Lucas","nameType":"Personal","givenName":"Lucas","familyName":"Pelkmans","affiliation":[],"nameIdentifiers":[]},{"name":"Krejci, Lumir","nameType":"Personal","givenName":"Lumir","familyName":"Krejci","affiliation":[],"nameIdentifiers":[]},{"name":"Ferrari, Stefano","nameType":"Personal","givenName":"Stefano","familyName":"Ferrari","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Sumoylation regulates EXO1 stability and processing of DNA damage"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Biophysics"},{"subject":"Biochemistry"},{"subject":"Cell Biology"},{"subject":"Genetics"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Biological sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Molecular Biology"},{"subject":"Developmental Biology"},{"subject":"Cancer"},{"subject":"111714 Mental Health","subjectScheme":"FOR"},{"subject":"FOS: Health sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Health sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"110309 Infectious Diseases","subjectScheme":"FOR"}],"contributors":[],"dates":[{"date":"2015-06-17","dateType":"Created"},{"date":"2019-06-03","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1080/15384101.2015.1060381","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["1707475 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"DNA double-strand break repair by the error-free pathway of homologous recombination (HR) requires the concerted action of several factors. Among these, EXO1 and DNA2/BLM are responsible for the extensive resection of DNA ends to produce 3′-overhangs, which are essential intermediates for downstream steps of HR. Here we show that EXO1 is a SUMO target and that sumoylation affects EXO1 ubiquitylation and protein stability. We identify an UBC9-PIAS1/PIAS4-dependent mechanism controlling human EXO1 sumoylation in vivo and demonstrate conservation of this mechanism in yeast by the Ubc9-Siz1/Siz2 using an in vitro reconstituted system. Furthermore, we show physical interaction between EXO1 and the de-sumoylating enzyme SENP6 both in vitro and in vivo, promoting EXO1 stability. Finally, we identify the major sites of sumoylation in EXO1 and show that ectopic expression of a sumoylation-deficient form of EXO1 rescues the DNA damage-induced chromosomal aberrations observed upon wt-EXO1 expression. Thus, our study identifies a novel layer of regulation of EXO1, making the pathways that regulate its function an ideal target for therapeutic intervention.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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