title: Base excision repair of 8-oxoG in dinucleosomes.
abstract: In this work we have studied the effect of chromatin structure on the base excision repair (BER) efficiency of 8-oxoG. As a model system we have used precisely positioned dinucleosomes assembled with linker histone H1. A single 8-oxoG was inserted either in the linker or the core particle DNA within the dinucleosomal template. We found that in the absence of histone H1 the glycosylase OGG1 removed 8-oxoG from the linker DNA and cleaved DNA with identical efficiency as in the naked DNA. In contrast, the presence of histone H1 resulted in close to 10-fold decrease in the efficiency of 8-oxoG initiation of repair in linker DNA independently of linker DNA length. The repair of 8-oxoG in nucleosomal DNA was very highly impeded in both absence and presence of histone H1. Chaperone-induced uptake of H1 restored the efficiency of the glycosylase induced removal of 8-oxoG from linker DNA, but not from the nucleosomal DNA. We show, however, that removal of histone H1 and nucleosome remodelling are both necessary and sufficient for an efficient removal of 8-oxoG in nucleosomal DNA. Finally, a model for BER of 8-oxoG in chromatin templates is suggested.
authors.affiliation: Université de Lyon, Laboratoire de Biologie Moléculaire de la Cellule, CNRS-UMR 5239, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon cedex 07, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Menoni
authors.forename: Manu Shubhdarshan
authors.initials: MS
authors.lastname: Shukla
authors.forename: Véronique
authors.initials: V
authors.lastname: Gerson
authors.forename: Stefan
authors.initials: S
authors.lastname: Dimitrov
authors.forename: Dimitar
authors.initials: D
authors.lastname: Angelov
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D056490:Nucleosome Assembly Protein 1 / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism*
chemical_list: D006657:Histones; D056490:Nucleosome Assembly Protein 1; D009707:Nucleosomes; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse