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Localisation et fonction du variant d'histone macroH2A

Abstract : MacroH2A (mH2A) is an unusual histone variant which consists of a histone-like domain and a non-histone region (NHR). Immunofluorescence data suggested that macroH2A is accumulated at the inactive X chromosome. In this work we have used chromatin immunoprecipitation (ChIP) analysis, combined with human and mouse genome-wide array hybridization (ChIP on CHIP), to investigate the association of mH2A with the inactive X chromosome. The mH2A enrichment is moderate, suggesting a non-essential mH2A participation to the X inactivation
We describe a novel function of mH2A, namely its involvement in DNA repair. In vivo mH2A1 nucleosomes are found associated with PARP-1 and in vitro experiments demonstrate that the NHR domain of mH2A1 is essential for this interaction. The siRNA suppression of the expression of mH2A1 affects cell survival after oxidative DNA damage and inhibition of PARP-1 enzymatic activity abolishes this effect. The absence of mH2A1 results in overactivation of PARP-1 and compromises severely DNA repair after oxidative damage. Rescue experiments with silent resistant mutants of mH2A1 evidence that the NHR, but not the H2A-like domain of mH2A1, is required for the efficient repair of DNA. These data show that the involvement of mH2A1 in the repair of DNA is realized through a PARP-1 repair pathway.
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https://tel.archives-ouvertes.fr/tel-00183255
Contributor : Flore Mietton <>
Submitted on : Monday, October 29, 2007 - 4:10:03 PM
Last modification on : Friday, November 6, 2020 - 3:48:16 AM
Long-term archiving on: : Monday, April 12, 2010 - 12:55:19 AM

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  • HAL Id : tel-00183255, version 1

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Flore Mietton. Localisation et fonction du variant d'histone macroH2A. Biochimie [q-bio.BM]. Université Joseph-Fourier - Grenoble I, 2007. Français. ⟨tel-00183255⟩

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