Gadd45, a p53-Responsive Stress Protein, Modifies DNA Accessibility on Damaged Chromatin - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Molecular and Cellular Biology Année : 1999

Gadd45, a p53-Responsive Stress Protein, Modifies DNA Accessibility on Damaged Chromatin

France Carrier
  • Fonction : Auteur
Philippe Georgel
Mellissa Blake
  • Fonction : Auteur
H. Udo Kontny
  • Fonction : Auteur
Michael Antinore
  • Fonction : Auteur
Marzia Gariboldi
  • Fonction : Auteur
Timothy Myers
  • Fonction : Auteur
Albert Fornace
  • Fonction : Auteur

Résumé

This report demonstrates that Gadd45, a p53-responsive stress protein, can facilitate topoisomerase relaxing and cleavage activity in the presence of core histones. A correlation between reduced expression of Gadd45 and increased resistance to topoisomerase I and topoisomerase II inhibitors in a variety of human cell lines was also found. Gadd45 could potentially mediate this effect by destabilizing histone-DNA interactions since it was found to interact directly with the four core histones. To evaluate this possibility, we investigated the effect of Gadd45 on preassembled mononucleosomes. Our data indicate that Gadd45 directly associates with mononucleosomes that have been altered by histone acetylation or UV radiation. This interaction resulted in increased DNase I accessibility on hyperacetylated mononucleosomes and substantial reduction of T4 endonuclease V accessibility to cyclobutane pyrimidine dimers on UV-irradiated mononucleosomes but not on naked DNA. Both histone acetylation and UV radiation are thought to destabilize the nucleosomal structure. Hence, these results imply that Gadd45 can recognize an altered chromatin state and modulate DNA accessibility to cellular proteins.

Dates et versions

inserm-02438260 , version 1 (14-01-2020)

Identifiants

Citer

France Carrier, Philippe Georgel, Philippe Pourquier, Mellissa Blake, H. Udo Kontny, et al.. Gadd45, a p53-Responsive Stress Protein, Modifies DNA Accessibility on Damaged Chromatin. Molecular and Cellular Biology, 1999, 19 (3), pp.1673-1685. ⟨10.1128/mcb.19.3.1673⟩. ⟨inserm-02438260⟩
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