title: DNA-damage response in chromatin of ribosomal genes and the surrounding genome.
abstract: DNA repair events have functional significance especially for genome stability. Although the DNA damage response within the whole genome has been extensively studied, the region-specific characteristics of nuclear sub-compartments such as the nucleolus or fragile sites have not been fully elucidated. Here, we show that the heterochromatin protein HP1 and PML protein recognize spontaneously occurring 53BP1- or γ-H2AX-positive DNA lesions throughout the genome. Moreover, 53BP1 nuclear bodies, which co-localize with PML bodies, also occur within the nucleoli compartments. Irradiation of the human osteosarcoma cell line U2OS with γ-rays increases the degree of co-localization between 53BP1 and PML bodies throughout the genome; however, the 53BP1 protein is less abundant in chromatin of ribosomal genes and fragile sites (FRA3B and FRA16D) in γ-irradiated cells. Most epigenomic marks on ribosomal genes and fragile sites are relatively stable in both non-irradiated and γ-irradiated cells. However, H3K4me2, H3K9me3, H3K27me3 and H3K79me1 were significantly changed in promoter and coding regions of ribosomal genes after exposure of cells to γ-rays. In fragile sites, γ-irradiation induces a decrease in H3K4me3, changes the levels of HP1β, and modifies the levels of H3K9 acetylation, while the level of H3K9me3 was relatively stable. In these studies, we confirm a specific DNA-damage response that differs between the ribosomal genes and fragile sites, which indicates the region-specificity of DNA repair.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Královopolská 135, CZ-612 65, Brno, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Foltánková
authors.forename: Soňa
authors.initials: S
authors.lastname: Legartová
authors.forename: Stanislav
authors.initials: S
authors.lastname: Kozubek
authors.forename: Michal
authors.initials: M
authors.lastname: Hofer
authors.forename: Eva
authors.initials: E
authors.lastname: Bártová
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism / Q000528:radiation effects; D043283:Chromosome Fragile Sites / Q000235:genetics*; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000528:radiation effects; D005347:Fibroblasts / Q000528:radiation effects; D005720:Gamma Rays; D042822:Genomic Instability; D006657:Histones / Q000528:radiation effects; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism / Q000528:radiation effects; D012516:Osteosarcoma; D000071156:Promyelocytic Leukemia Protein; D012270:Ribosomes / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism / Q000528:radiation effects; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000528:radiation effects; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: C000715593:CBX1 protein, human; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; C498302:Trp53bp1 protein, mouse; D025521:Tumor Suppressor Proteins; D000071857:Tumor Suppressor p53-Binding Protein 1; D000090266:Chromobox Protein Homolog 5