DNA-damage response in chromatin of ribosomal genes and the surrounding genome
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
23566839
DOI
10.1016/j.gene.2013.03.108
PII: S0378-1119(13)00402-2
Knihovny.cz E-resources
- MeSH
- Tumor Suppressor p53-Binding Protein 1 MeSH
- Chromatin genetics MeSH
- Chromosomal Proteins, Non-Histone metabolism radiation effects MeSH
- DNA-Binding Proteins radiation effects MeSH
- Fibroblasts radiation effects MeSH
- Chromosome Fragile Sites genetics MeSH
- Histones radiation effects MeSH
- Chromobox Protein Homolog 5 MeSH
- Nuclear Proteins metabolism radiation effects MeSH
- Humans MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Tumor Suppressor Proteins metabolism radiation effects MeSH
- Genomic Instability MeSH
- DNA Repair genetics MeSH
- Osteosarcoma MeSH
- DNA Damage radiation effects MeSH
- Promyelocytic Leukemia Protein MeSH
- Ribosomes genetics MeSH
- Transcription Factors metabolism radiation effects MeSH
- Gamma Rays MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Tumor Suppressor p53-Binding Protein 1 MeSH
- CBX1 protein, human MeSH Browser
- Chromatin MeSH
- Chromosomal Proteins, Non-Histone MeSH
- DNA-Binding Proteins MeSH
- Histones MeSH
- Chromobox Protein Homolog 5 MeSH
- Nuclear Proteins MeSH
- Tumor Suppressor Proteins MeSH
- Pml protein, mouse MeSH Browser
- Promyelocytic Leukemia Protein MeSH
- Transcription Factors MeSH
- Trp53bp1 protein, mouse MeSH Browser
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.
References provided by Crossref.org
HP1β-dependent recruitment of UBF1 to irradiated chromatin occurs simultaneously with CPDs
