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Genotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage

2012-11Journal article Open access
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dc.contributor.authorMadureira, Patricia A.
dc.contributor.authorHill, Richard
dc.contributor.authorLee, Patrick W. K.
dc.contributor.authorWaisman, David M.
dc.date.accessioned2018-12-07T14:57:58Z
dc.date.available2018-12-07T14:57:58Z
dc.date.issued2012-11
dc.description.abstractAnnexin A2 is an abundant cellular protein that is mainly localized in the cytoplasm and plasma membrane, however a small population has been found in the nucleus, suggesting a nuclear function for the protein. Annexin A2 possesses a nuclear export sequence (NES) and inhibition of the NES is sufficient to cause nuclear accumulation. Here we show that annexin A2 accumulates in the nucleus in response to genotoxic agents including gamma-radiation, UV radiation, etoposide and chromium VI and that this event is mediated by the nuclear export sequence of annexin A2. Nuclear accumulation of annexin A2 is blocked by the antioxidant agent N-acetyl cysteine (NAC) and stimulated by hydrogen peroxide (H2O2), suggesting that this is a reactive oxygen species dependent event. In response to genotoxic agents, cells depleted of annexin A2 show enhanced phospho-histone H2AX and p53 levels, increased numbers of p53-binding protein 1 nuclear foci and increased levels of nuclear 8-oxo-2'-deoxyguanine, suggesting that annexin A2 plays a role in protecting DNA from damage. This is the first report showing the nuclear translocation of annexin A2 in response to genotoxic agents and its role in mitigating DNA damage.
dc.description.sponsorshipNatural Sciences and Engineering Research Council of Canada (NSERC); European Union [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Beatrice Hunter Cancer Research Institute; Terry Fox Foundation
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1371/journal.pone.0050591
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10400.1/11788
dc.language.isoeng
dc.peerreviewedyes
dc.publisherPublic Library of Science
dc.relationWORK PLAN FOR RESEARCH FELLOWSHIP PCOFUND-GA-2009-246542
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectOxidative stress
dc.subjectTyrosine kinase
dc.subjectIi tetramer
dc.subjectCa2+-binding sites
dc.subjectCellular-response
dc.subjectCrystal-structure
dc.subjectProtein-kinases
dc.subjectExport signal
dc.subjectHistone H2Ax
dc.subjectCalpactin-I
dc.titleGenotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleWORK PLAN FOR RESEARCH FELLOWSHIP PCOFUND-GA-2009-246542
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBI%2F52182%2F2013/PT
oaire.citation.issue11
oaire.citation.startPagee50591
oaire.citation.titlePLoS ONE
oaire.citation.volume7
person.familyNameMadureira
person.familyNameHill
person.givenNamePatricia
person.givenNameRichard
person.identifier.ciencia-id6612-9A86-6929
person.identifier.orcid0000-0002-4856-3908
person.identifier.orcid0000-0003-0394-6048
person.identifier.scopus-author-id10340140500
person.identifier.scopus-author-id55266604200
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublicationa40de6a3-d52d-45dd-8620-cb94a22ebc8f
relation.isAuthorOfPublicatione67f4a4f-aa35-4740-87b0-0cd07a9e1993
relation.isAuthorOfPublication.latestForDiscoverye67f4a4f-aa35-4740-87b0-0cd07a9e1993
relation.isProjectOfPublication976621e4-7a18-46a8-af37-c0a4e4b78ca3
relation.isProjectOfPublication.latestForDiscovery976621e4-7a18-46a8-af37-c0a4e4b78ca3

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