{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:55:25Z","timestamp":1762102525234,"version":"build-2065373602"},"reference-count":74,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:00:00Z","timestamp":1595980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["PTDC\/BTM-TEC\/29843\/2017","Institute of Biomedicine (iBiMED)\u2014UID\/BIM\/04501\/2020 and POCI-01-0145-FEDER-007628"],"award-info":[{"award-number":["PTDC\/BTM-TEC\/29843\/2017","Institute of Biomedicine (iBiMED)\u2014UID\/BIM\/04501\/2020 and POCI-01-0145-FEDER-007628"]}]},{"name":"Centro Regional Centro","award":["CENTRO-01-0145-FEDER-000003"],"award-info":[{"award-number":["CENTRO-01-0145-FEDER-000003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Lamina-associated polypeptide 1 (LAP1) is a nuclear envelope (NE) protein whose function remains poorly characterized. In a recent LAP1 protein interactome study, a putative regulatory role in the DNA damage response (DDR) has emerged and telomeric repeat-binding factor 2 (TRF2), a protein intimately associated with this signaling pathway, was among the list of LAP1 interactors. To gain insights into LAP1\u2032s physiological properties, the interaction with TRF2 in human cells exposed to DNA-damaging agents was investigated. The direct LAP1:TRF2 binding was validated in vitro by blot overlay and in vivo by co-immunoprecipitation after hydrogen peroxide and bleomycin treatments. The regulation of this protein interaction by LAP1 phosphorylation was demonstrated by co-immunoprecipitation and mass spectrometry following okadaic acid exposure. The involvement of LAP1 and TRF2 in the DDR was confirmed by their increased nuclear protein levels after bleomycin treatment, evaluated by immunoblotting, as well as by their co-localization with DDR factors at the NE and within the nucleoplasm, assessed by immunocytochemistry. Effectively, we showed that the LAP1:TRF2 complex is established during a cellular response against DNA damage. This work proposes a novel functional role for LAP1 in the DDR, revealing a potential biological mechanism that may be disrupted in LAP1-associated pathologies.<\/jats:p>","DOI":"10.3390\/cells9081804","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T03:36:38Z","timestamp":1596080198000},"page":"1804","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Nuclear Accumulation of LAP1:TRF2 Complex during DNA Damage Response Uncovers a Novel Role for LAP1"],"prefix":"10.3390","volume":"9","author":[{"given":"C\u00e1tia D.","family":"Pereira","sequence":"first","affiliation":[{"name":"Neuroscience and Signaling Laboratory, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3277-1809","authenticated-orcid":false,"given":"Filipa","family":"Martins","sequence":"additional","affiliation":[{"name":"Neuroscience and Signaling Laboratory, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2343-2215","authenticated-orcid":false,"given":"Mariana","family":"Santos","sequence":"additional","affiliation":[{"name":"Neuroscience and Signaling Laboratory, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Thorsten","family":"M\u00fceller","sequence":"additional","affiliation":[{"name":"Cell Signaling in Neurodegeneration (CSIN), Medical Proteome-Center, Ruhr-University Bochum, 44801 Bochum, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3718-9874","authenticated-orcid":false,"given":"Odete A. B.","family":"da Cruz e Silva","sequence":"additional","affiliation":[{"name":"Neuroscience and Signaling Laboratory, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5862-5797","authenticated-orcid":false,"given":"Sandra","family":"Rebelo","sequence":"additional","affiliation":[{"name":"Neuroscience and Signaling Laboratory, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/nrm.2016.153","article-title":"Mechanisms and functions of nuclear envelope remodelling","volume":"18","author":"Ungricht","year":"2017","journal-title":"Nat. Rev. Mol. 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