DNA repair defects ascribed to pby1 are caused by disruption of Holliday junction resolvase Mus81-Mms4 |
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| Affiliation: | 1. Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, United Kingdom;2. Infection, Immunology Inflammation & Physiological Medicine, UCL Great Ormond Street Institute of Child Health, WC1N 1EH London, United Kingdom;3. Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, United States;4. National Institute of General Medical Sciences, National Institutes of Health, Bethesda, MA 20892, United States;5. Department of Genetics, University Medical Center Utrecht, 3584, the Netherlands;6. Centre for Endocrinology, William Harvey Research Institute, Barts & The London Medical School, Queen Mary University of London, EC1M 6BQ, United Kingdom;7. NIHR Biomedical Research Centre at Great Ormond Street Hospital, Children NHS Foundation Trust and UCL, London WC1N 1EH, United Kingdom;8. Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, United States;9. The Francis Crick Institute, London NW1 1ST, United Kingdom |
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| Abstract: | PBY1 continues to be linked with DNA repair through functional genomics studies in yeast. Using the yeast knockout (YKO) strain collection, high-throughput genetic interaction screens have identified a large set of negative interactions between PBY1 and genes involved in genome stability. In drug sensitivity screens, the YKO collection pby1Δ strain exhibits a sensitivity profile typical for genes involved in DNA replication and repair. We show that these findings are not related to loss of Pby1. On the basis of genetic interaction profile similarity, we pinpoint disruption of Holliday junction resolvase Mus81-Mms4 as the mutation responsible for DNA repair phenotypes currently ascribed to pby1. The finding that Pby1 is not a DNA repair factor reconciles discrepancies in the data available for PBY1, and indirectly supports a role for Pby1 in mRNA metabolism. Data that has been collected using the YKO collection pby1Δ strain confirms and expands the chemical-genetic interactome of MUS81-MMS4. |
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| Keywords: | P body Holliday junction resolvase INO80 chromatin remodeling complex |
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