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dc.contributor.authorVan Loon, Barbara
dc.contributor.authorSamson, Leona D
dc.date.accessioned2015-10-29T17:55:28Z
dc.date.available2015-10-29T17:55:28Z
dc.date.issued2013-01
dc.date.submitted2012-11
dc.identifier.issn15687864
dc.identifier.urihttp://hdl.handle.net/1721.1/99514
dc.description.abstractDue to a harsh environment mitochondrial genomes accumulate high levels of DNA damage, in particular oxidation, hydrolytic deamination, and alkylation adducts. While repair of alkylated bases in nuclear DNA has been explored in detail, much less is known about the repair of DNA alkylation damage in mitochondria. Alkyladenine DNA glycosylase (AAG) recognizes and removes numerous alkylated bases, but to date AAG has only been detected in the nucleus, even though mammalian mitochondria are known to repair DNA lesions that are specific substrates of AAG. Here we use immunofluorescence to show that AAG localizes to mitochondria, and we find that native AAG is present in purified human mitochondrial extracts, as well as that exposure to alkylating agent promotes AAG accumulation in the mitochondria. We identify mitochondrial single-stranded binding protein (mtSSB) as a novel interacting partner of AAG; interaction between mtSSB and AAG is direct and increases upon methyl methanesulfonate (MMS) treatment. The consequence of this interaction is specific inhibition of AAG glycosylase activity in the context of a single-stranded DNA (ssDNA), but not a double-stranded DNA (dsDNA) substrate. By inhibiting AAG-initiated processing of damaged bases, mtSSB potentially prevents formation of DNA breaks in ssDNA, ensuring that base removal primarily occurs in dsDNA. In summary, our findings suggest the existence of AAG-initiated BER in mitochondria and further support a role for mtSSB in DNA repair.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant CA055042)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant ES002109)en_US
dc.description.sponsorshipUniversity of Zurichen_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.dnarep.2012.11.009en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleAlkyladenine DNA glycosylase (AAG) localizes to mitochondria and interacts with mitochondrial single-stranded binding protein (mtSSB)en_US
dc.typeArticleen_US
dc.identifier.citationVan Loon, Barbara, and Leona D. Samson. “Alkyladenine DNA Glycosylase (AAG) Localizes to Mitochondria and Interacts with Mitochondrial Single-Stranded Binding Protein (mtSSB).” DNA Repair 12, no. 3 (March 2013): 177–187.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Center for Environmental Health Sciencesen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorvan Loon, Barbaraen_US
dc.contributor.mitauthorSamson, Leona D.en_US
dc.relation.journalDNA Repairen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsvan Loon, Barbara; Samson, Leona D.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-7112-1454
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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