Global Genome-Nucleotide Excision Repair is Organised into Domains Promoting Efficient DNA Repair in Chromatin

ABSTRACT: The rates at which lesions are removed by DNA repair can vary widely throughout the genome with important implications for genomic stability. We measured the distribution of nucleotide excision repair (NER) rates for UV induced lesions throughout the yeast genome. By plotting these repair rates in relation to all ORFs and their associated flanking sequences, we reveal that in normal cells, genomic repair rates display a distinctive pattern, suggesting that DNA repair is highly organised within the genome. We compared genome-wide DNA repair rates in wild type and in RAD16 deleted cells, which are defective in the global genome-NER (GG-NER) sub-pathway, demonstrating how this alters the normal
distribution of NER rates throughout the genome. We examine the genomic locations of global genome NER factor binding in chromatin before and after UV irradiation, and reveal that GG-NER is organized and initiated from specific locations. By controlling the chromatin occupancy of the histone acetyl transferase Gcn5, the GG-NER complex regulates the histone H3 acetylation status and chromatin structure in the vicinity of these genomic sites to promote the efficient DNA repair of UV induced lesions. This demonstrates that chromatin remodeling during the GG-NER process is organized into domains in the genome. Importantly, we demonstrate that deleting the histone modifier GCN5, an accessory factor required for chromatin remodeling during GG-NER, significantly alters the genomic distribution of NER rates. These observations could have important implications for the effect of histone and chromatin modifiers on the distribution of genomic mutations acquired throughout the genome.

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Simon Reed 

PROVIDER: E-MTAB-4641 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress