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Identification of a novel DNA oxidative damage repair pathway, requiring the ubiquitination of the histone variant macroH2A1.1.
Ouararhni, Khalid; Mietton, Flore; Sabir, Jamal S M; Ibrahim, Abdulkhaleg; Molla, Annie; Albheyri, Raed S; Zari, Ali T; Bahieldin, Ahmed; Menoni, Hervé; Bronner, Christian; Dimitrov, Stefan; Hamiche, Ali.
Afiliación
  • Ouararhni K; Département de Génomique Fonctionnelle Et Cancer, Institut de Génétique Et Biologie Moléculaire Et Cellulaire (IGBMC), Université de Strasbourg/CNRS/INSERM, Equipe Labellisée La Ligue Nationale Contre Le Cancer, 67404, Illkirch Cedex, France.
  • Mietton F; Institute for Advanced Biosciences, Inserm U 1209, CNRS UMR 5309, Université Grenoble Alpes, 38000, Grenoble, France.
  • Sabir JSM; Centre of Excellence in Bionanoscience Research, King Abdulaziz University, Jeddah, Saudi Arabia.
  • Ibrahim A; Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
  • Molla A; Département de Génomique Fonctionnelle Et Cancer, Institut de Génétique Et Biologie Moléculaire Et Cellulaire (IGBMC), Université de Strasbourg/CNRS/INSERM, Equipe Labellisée La Ligue Nationale Contre Le Cancer, 67404, Illkirch Cedex, France.
  • Albheyri RS; National Research Centre for Tropical and Transboundary Diseases (NRCTTD), Alzentan, 99316, Libya.
  • Zari AT; Institute for Advanced Biosciences, Inserm U 1209, CNRS UMR 5309, Université Grenoble Alpes, 38000, Grenoble, France.
  • Bahieldin A; Centre of Excellence in Bionanoscience Research, King Abdulaziz University, Jeddah, Saudi Arabia.
  • Menoni H; Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
  • Bronner C; Centre of Excellence in Bionanoscience Research, King Abdulaziz University, Jeddah, Saudi Arabia.
  • Dimitrov S; Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
  • Hamiche A; Centre of Excellence in Bionanoscience Research, King Abdulaziz University, Jeddah, Saudi Arabia.
BMC Biol ; 22(1): 188, 2024 Sep 02.
Article en En | MEDLINE | ID: mdl-39218869
ABSTRACT

BACKGROUND:

The histone variant macroH2A (mH2A), the most deviant variant, is about threefold larger than the conventional histone H2A and consists of a histone H2A-like domain fused to a large Non-Histone Region responsible for recruiting PARP-1 to chromatin. The available data suggest that the histone variant mH2A participates in the regulation of transcription, maintenance of heterochromatin, NAD+ metabolism, and double-strand DNA repair.

RESULTS:

Here, we describe a novel function of mH2A, namely its implication in DNA oxidative damage repair through PARP-1. The depletion of mH2A affected both repair and cell survival after the induction of oxidative lesions in DNA. PARP-1 formed a specific complex with mH2A nucleosomes in vivo. The mH2A nucleosome-associated PARP-1 is inactive. Upon oxidative damage, mH2A is ubiquitinated, PARP-1 is released from the mH2A nucleosomal complex, and is activated. The in vivo-induced ubiquitination of mH2A, in the absence of any oxidative damage, was sufficient for the release of PARP-1. However, no release of PARP-1 was observed upon treatment of the cells with either the DNA alkylating agent MMS or doxorubicin.

CONCLUSIONS:

Our data identify a novel pathway for the repair of DNA oxidative lesions, requiring the ubiquitination of mH2A for the release of PARP-1 from chromatin and its activation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño del ADN / Histonas / Reparación del ADN / Ubiquitinación / Poli(ADP-Ribosa) Polimerasa-1 Límite: Humans Idioma: En Revista: BMC Biol Asunto de la revista: BIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño del ADN / Histonas / Reparación del ADN / Ubiquitinación / Poli(ADP-Ribosa) Polimerasa-1 Límite: Humans Idioma: En Revista: BMC Biol Asunto de la revista: BIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido