RNase H enables efficient repair of R-loop induced DNA damage
| Autor: | Douglas Koshland, Jeremy D. Amon |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genome instability DNA Repair R-loop Mutant S. cerevisiae rDNA DNA polymerase delta break-induced replication 0302 clinical medicine Biology (General) genes 0303 health sciences biology Chemistry General Neuroscience General Medicine R-loops Cell biology Genes and Chromosomes 030220 oncology & carcinogenesis HIV/AIDS Medicine DNA mismatch repair Research Article chromosomes RNase H DNA repair DNA damage QH301-705.5 DNA polymerase II Science Ribonuclease H Saccharomyces cerevisiae General Biochemistry Genetics and Molecular Biology 03 medical and health sciences RNA polymerase I Genetics Ribosomal DNA Replication protein A 030304 developmental biology General Immunology and Microbiology Human Genome Molecular biology genome instability 030104 developmental biology biology.protein Biochemistry and Cell Biology 030217 neurology & neurosurgery Nucleotide excision repair DNA Damage |
| Zdroj: | eLife, Vol 5 (2016) eLife |
| Popis: | R-loops, three-stranded structures that form when transcripts hybridize to chromosomal DNA, are potent agents of genome instability. This instability has been explained by the ability of R-loops to induce DNA damage. Here, we show that persistent R-loops also compromise DNA repair. Depleting endogenous RNase H activity impairs R-loop removal in budding yeast, causing DNA damage that occurs preferentially in the repetitive ribosomal DNA locus (rDNA). We analyzed the repair kinetics of this damage and identified mutants that modulate repair. Our results indicate that persistent R-loops in the rDNA induce damage that is slowly repaired by break-induced replication (BIR). Furthermore, R-loop induced BIR at the rDNA leads to lethal repair intermediates when RNA polymerase I elongation is compromised. We present a model to explain how removal of R-loops by RNase H is critical in ensuring the efficient repair of R-loop induced DNA damage by pathways other than BIR. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|