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The protein phosphatase EYA4 promotes homologous recombination (HR) through dephosphorylation of tyrosine 315 on RAD51.
de la Peña Avalos, Bárbara; Paquet, Nicolas; Tropée, Romain; Coulombe, Yan; Palacios, Hannah; Leung, Justin W; Masson, Jean-Yves; Duijf, Pascal H G; Dray, Eloïse.
Afiliação
  • de la Peña Avalos B; Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
  • Paquet N; Mays Cancer Center at UT Health San Antonio MD Anderson, San Antonio, TX, USA.
  • Tropée R; Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
  • Coulombe Y; Queensland University of Technology, Translational Research Institute, Brisbane, QLD, Australia.
  • Palacios H; Genome Stability Laboratory, CHU de Québec Research Center, HDQ Pavilion, Oncology Division, Québec City, QC, Canada.
  • Leung JW; Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, Québec City, QC, Canada.
  • Masson JY; Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
  • Duijf PHG; Department of Radiation Oncology, University of Texas Health and Science Center, San Antonio, TX 78229, USA.
  • Dray E; Genome Stability Laboratory, CHU de Québec Research Center, HDQ Pavilion, Oncology Division, Québec City, QC, Canada.
Nucleic Acids Res ; 52(3): 1173-1187, 2024 Feb 09.
Article em En | MEDLINE | ID: mdl-38084915
Efficient DNA repair and limitation of genome rearrangements rely on crosstalk between different DNA double-strand break (DSB) repair pathways, and their synchronization with the cell cycle. The selection, timing and efficacy of DSB repair pathways are influenced by post-translational modifications of histones and DNA damage repair (DDR) proteins, such as phosphorylation. While the importance of kinases and serine/threonine phosphatases in DDR have been extensively studied, the role of tyrosine phosphatases in DNA repair remains poorly understood. In this study, we have identified EYA4 as the protein phosphatase that dephosphorylates RAD51 on residue Tyr315. Through its Tyr phosphatase activity, EYA4 regulates RAD51 localization, presynaptic filament formation, foci formation, and activity. Thus, it is essential for homologous recombination (HR) at DSBs. DNA binding stimulates EYA4 phosphatase activity. Depletion of EYA4 decreases single-stranded DNA accumulation following DNA damage and impairs HR, while overexpression of EYA4 in cells promotes dephosphorylation and stabilization of RAD51, and thereby nucleoprotein filament formation. Our data have implications for a pathological version of RAD51 in EYA4-overexpressing cancers.
Assuntos

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Transativadores / Rad51 Recombinase Limite: Humans Idioma: En Revista: Nucleic Acids Res Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Transativadores / Rad51 Recombinase Limite: Humans Idioma: En Revista: Nucleic Acids Res Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos