Nuclear WRAP53 promotes neuronal survival and functional recovery after stroke
Failure of neurons to efficiently repair DNA double-strand breaks (DSBs) contributes to cerebral damage after stroke. However, the molecular machinery that regulates DNA repair in this neurological disorder is unknown. Here, we found that DSBs in oxygen/glucose-deprived (OGD) neurons spatiotemporall...
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| Veröffentlicht in: | Science advances 2020-10, Vol.6 (41) |
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| container_title | Science advances |
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| creator | Sánchez-Morán, Irene Rodríguez, Cristina Lapresa, Rebeca Agulla, Jesús Sobrino, Tomás Castillo, José Bolaños, Juan P Almeida, Angeles |
| description | Failure of neurons to efficiently repair DNA double-strand breaks (DSBs) contributes to cerebral damage after stroke. However, the molecular machinery that regulates DNA repair in this neurological disorder is unknown. Here, we found that DSBs in oxygen/glucose-deprived (OGD) neurons spatiotemporally correlated with the up-regulation of WRAP53 (WD40-encoding p53-antisense RNA), which translocated to the nucleus to activate the DSB repair response. Mechanistically, OGD triggered a burst in reactive oxygen species that induced both DSBs and translocation of WRAP53 to the nucleus to promote DNA repair, a pathway that was confirmed in an in vivo mouse model of stroke. Noticeably, nuclear translocation of WRAP53 occurred faster in OGD neurons expressing the
human nonsynonymous single-nucleotide polymorphism (SNP) rs2287499 (c.202C>G). Patients carrying this SNP showed less infarct volume and better functional outcome after stroke. These results indicate that WRAP53 fosters DNA repair and neuronal survival to promote functional recovery after stroke. |
| doi_str_mv | 10.1126/sciadv.abc5702 |
| format | Article |
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human nonsynonymous single-nucleotide polymorphism (SNP) rs2287499 (c.202C>G). Patients carrying this SNP showed less infarct volume and better functional outcome after stroke. These results indicate that WRAP53 fosters DNA repair and neuronal survival to promote functional recovery after stroke.</description><subject>Animals</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell Survival - genetics</subject><subject>Cellular Biology</subject><subject>DNA Repair</subject><subject>Glucose - metabolism</subject><subject>Humans</subject><subject>Mice</subject><subject>Molecular Chaperones - metabolism</subject><subject>Neurons - metabolism</subject><subject>SciAdv r-articles</subject><subject>Stroke - genetics</subject><subject>Stroke - metabolism</subject><subject>Telomerase - metabolism</subject><subject>Transcription Factors - metabolism</subject><issn>2375-2548</issn><issn>2375-2548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUctOwzAQtBCIVqVXjihHLi22Yyf2BamqeElVQQjE0do4NgSSuNhJpP49KS1VOe1od3ZmtYPQOcFTQmhyFXQBeTeFTPMU0yM0pHHKJ5QzcXyAB2gcwifGmLAk4USeokEcYyo4lUO0XLa6NOCjt-fZE4-jlXeVa0yIatN6V0MZhdZ3RdcDqPPItrVuit--N9p1xq8jsI3xUWi8-zJn6MRCGcx4V0fo9fbmZX4_WTzePcxni4mOJW4mMrN5KkWWArW4BynmnEOiQWMhgRnJJQOacEokZoILzSThNsulgNRSIeIRut7qrtqsMrk2deOhVCtfVODXykGh_k_q4kO9u06lnBGcJL3A5U7Au-_WhEZVRdCmLKE2rg2KMiZpQmO68Zpuqdq7ELyxexuC1SYHtc1B7XLoFy4Oj9vT_74e_wDFGYZ0</recordid><startdate>20201001</startdate><enddate>20201001</enddate><creator>Sánchez-Morán, Irene</creator><creator>Rodríguez, Cristina</creator><creator>Lapresa, Rebeca</creator><creator>Agulla, Jesús</creator><creator>Sobrino, Tomás</creator><creator>Castillo, José</creator><creator>Bolaños, Juan P</creator><creator>Almeida, Angeles</creator><general>American Association for the Advancement of Science</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8901-3972</orcidid><orcidid>https://orcid.org/0000-0003-0485-8904</orcidid><orcidid>https://orcid.org/0000-0002-6685-3001</orcidid><orcidid>https://orcid.org/0000-0003-1588-5801</orcidid><orcidid>https://orcid.org/0000-0002-3949-6862</orcidid><orcidid>https://orcid.org/0000-0001-9574-2549</orcidid><orcidid>https://orcid.org/0000-0002-5144-7000</orcidid></search><sort><creationdate>20201001</creationdate><title>Nuclear WRAP53 promotes neuronal survival and functional recovery after stroke</title><author>Sánchez-Morán, Irene ; 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However, the molecular machinery that regulates DNA repair in this neurological disorder is unknown. Here, we found that DSBs in oxygen/glucose-deprived (OGD) neurons spatiotemporally correlated with the up-regulation of WRAP53 (WD40-encoding p53-antisense RNA), which translocated to the nucleus to activate the DSB repair response. Mechanistically, OGD triggered a burst in reactive oxygen species that induced both DSBs and translocation of WRAP53 to the nucleus to promote DNA repair, a pathway that was confirmed in an in vivo mouse model of stroke. Noticeably, nuclear translocation of WRAP53 occurred faster in OGD neurons expressing the
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| subjects | Animals Cell Nucleus - metabolism Cell Survival - genetics Cellular Biology DNA Repair Glucose - metabolism Humans Mice Molecular Chaperones - metabolism Neurons - metabolism SciAdv r-articles Stroke - genetics Stroke - metabolism Telomerase - metabolism Transcription Factors - metabolism |
| title | Nuclear WRAP53 promotes neuronal survival and functional recovery after stroke |
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