HJURP is recruited to double-strand break sites and facilitates DNA repair by promoting chromatin reorganization

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Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorDana-Farber Cancer Institute-
Autor(es): dc.contributorCenter for Cell-Based Therapy-CEPID/FAPESP-
Autor(es): dc.creatorSerafim, Rodolfo B.-
Autor(es): dc.creatorCardoso, Cibele-
Autor(es): dc.creatorStorti, Camila B.-
Autor(es): dc.creatorda Silva, Patrick-
Autor(es): dc.creatorQi, Hongyun-
Autor(es): dc.creatorParasuram, Ramya-
Autor(es): dc.creatorNavegante, Geovana-
Autor(es): dc.creatorPeron, Jean Pierre S.-
Autor(es): dc.creatorSilva, Wilson A.-
Autor(es): dc.creatorEspreafico, Enilza M.-
Autor(es): dc.creatorPaçó-Larson, Maria L.-
Autor(es): dc.creatorPrice, Brendan D.-
Autor(es): dc.creatorValente, Valeria-
Data de aceite: dc.date.accessioned2025-08-21T18:55:46Z-
Data de disponibilização: dc.date.available2025-08-21T18:55:46Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2024-03-07-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1038/s41388-024-02937-1-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/304300-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/304300-
Descrição: dc.descriptionHJURP is overexpressed in several cancer types and strongly correlates with patient survival. However, the mechanistic basis underlying the association of HJURP with cancer aggressiveness is not well understood. HJURP promotes the loading of the histone H3 variant, CENP-A, at the centromeric chromatin, epigenetically defining the centromeres and supporting proper chromosome segregation. In addition, HJURP is associated with DNA repair but its function in this process is still scarcely explored. Here, we demonstrate that HJURP is recruited to DSBs through a mechanism requiring chromatin PARylation and promotes epigenetic alterations that favor the execution of DNA repair. Incorporation of HJURP at DSBs promotes turnover of H3K9me3 and HP1, facilitating DNA damage signaling and DSB repair. Moreover, HJURP overexpression in glioma cell lines also affected global structure of heterochromatin independently of DNA damage induction, promoting genome-wide reorganization and assisting DNA damage response. HJURP overexpression therefore extensively alters DNA damage signaling and DSB repair, and also increases radioresistance of glioma cells. Importantly, HJURP expression levels in tumors are also associated with poor response of patients to radiation. Thus, our results enlarge the understanding of HJURP involvement in DNA repair and highlight it as a promising target for the development of adjuvant therapies that sensitize tumor cells to irradiation.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionDepartment of Cellular and Molecular Biology Ribeirão Preto Medical School University of São Paulo (USP), Avenida Bandeirantes-
Descrição: dc.descriptionSão Paulo State University (UNESP) School of Pharmaceutical Sciences, Rodovia Araraquara - Jaú, Km 01 - s/n, Campos Ville, SP-
Descrição: dc.descriptionDepartment of Radiation Oncology Dana-Farber Cancer Institute-
Descrição: dc.descriptionCenter for Cell-Based Therapy-CEPID/FAPESP, Rua Tenente Catão Roxo, 2501-
Descrição: dc.descriptionDepartment of Genetics Ribeirão Preto Medical School University of São Paulo (USP), Avenida Bandeirantes, 3900-
Descrição: dc.descriptionDepartment of Immunology Institute of Biomedical Sciences University of São Paulo, SP-
Descrição: dc.descriptionSão Paulo State University (UNESP) School of Pharmaceutical Sciences, Rodovia Araraquara - Jaú, Km 01 - s/n, Campos Ville, SP-
Formato: dc.format804-820-
Idioma: dc.languageen-
Relação: dc.relationOncogene-
???dc.source???: dc.sourceScopus-
Título: dc.titleHJURP is recruited to double-strand break sites and facilitates DNA repair by promoting chromatin reorganization-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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