Rad18 is required for DNA repair and checkpoint responses in fission yeast
| Autor: | Matthew J. O'Connell, Howard D. Lindsay, Heather Verkade, Anthony M. Carr, Sarah J. Bugg |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
G2 Phase
Saccharomyces cerevisiae Proteins DNA Repair DNA damage DNA repair Genes Fungal Gene Dosage Mitosis medicine.disease_cause Article Fungal Proteins Adenosine Triphosphate Suppression Genetic Schizosaccharomyces medicine CHEK1 Phosphorylation Molecular Biology Alleles Genetics Mutation Binding Sites biology Cell Cycle Nuclear Proteins Cell Biology G2-M DNA damage checkpoint biology.organism_classification Chromatin Proliferating cell nuclear antigen DNA-Binding Proteins DNA Topoisomerases Type II Schizosaccharomyces pombe Checkpoint Kinase 1 biology.protein Chromosomes Fungal Protein Kinases DNA Damage |
| Zdroj: | Molecular biology of the cell. 10(9) |
| ISSN: | 1059-1524 |
| Popis: | To survive damage to the genome, cells must respond by activating both DNA repair and checkpoint responses. Using genetic screens in the fission yeast Schizosaccharomyces pombe, we recently isolated new genes required for DNA damage checkpoint control. We show here that one of these strains defines a new allele of the previously described rad18 gene, rad18-74. rad18 is an essential gene, even in the absence of extrinsic DNA damage. It encodes a conserved protein related to the structural maintenance of chromosomes proteins. Point mutations in rad18 lead to defective DNA repair pathways responding to both UV-induced lesions and, as we show here, double-stranded breaks. Furthermore, rad18p is required to maintain cell cycle arrest in the presence of DNA damage, and failure of this leads to highly aberrant mitoses. A gene encoding a BRCT-containing protein, brc1, was isolated as an allele-specific high-copy suppressor of rad18-74. brc1is required for mitotic fidelity and for cellular viability in strains with rad18 mutations but is not essential for DNA damage responses. Mutations in rad18 and brc1are synthetically lethal with a topoisomerase II mutant (top2-191), indicating that these proteins play a role in chromatin organization. These studies show a role for chromatin organization in the maintenance or activation of responses to DNA damage. |
| Databáze: | OpenAIRE |
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