Journal article
Genetic investigation of formaldehyde-induced DNA damage response in Schizosaccharomyces pombe
Current genetics, v 66(3), pp 593-605
Jun 2020
PMID: 32034465
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Formaldehyde is a common environmental pollutant and is associated with adverse health effects. Formaldehyde is also considered to be a carcinogen because it can form DNA adducts, leading to genomic instability. How these adducts are prevented and removed is not fully understood. In this study, we used the fission yeast Schizosaccharomyces pombe as a model organism to investigate cellular tolerance pathways against formaldehyde exposure. We show that Fmd1 is a major formaldehyde dehydrogenase that functions to detoxify formaldehyde and that Fmd1 is critical to minimize formaldehyde-mediated DNA lesions. Our investigation revealed that nucleotide excision repair and homologous recombination have major roles in cellular tolerance to formaldehyde, while mutations in the Fanconi anemia, translesion synthesis, and base excision repair pathways also render cells sensitive to formaldehyde. We also demonstrate that loss of Wss1 or Wss2, proteases involved in the removal of DNA-protein crosslinks, sensitizes cells to formaldehyde and leads to replication defects. These results suggest that formaldehyde generates a variety of DNA lesions, including interstrand crosslinks, DNA-protein crosslinks, and base adducts. Thus, our genetic studies provide a framework for future investigation regarding health effects resulting from formaldehyde exposure.
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Details
- Title
- Genetic investigation of formaldehyde-induced DNA damage response in Schizosaccharomyces pombe
- Creators
- Vinesh Anandarajan - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245 N. 15th Street, Philadelphia, PA, 19102, USAChiaki Noguchi - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245 N. 15th Street, Philadelphia, PA, 19102, USAJulia Oleksak - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245 N. 15th Street, Philadelphia, PA, 19102, USAGrant Grothusen - School of Medicine, Cell and Molecular Biology Graduate Program, University of Pennsylvania, Philadelphia, PA, USADaniel Terlecky - West Chester University of Pennsylvania, Environmental Health Graduate Program, Philadelphia, PA, USAEishi Noguchi - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245 N. 15th Street, Philadelphia, PA, 19102, USA. en34@drexel.edu
- Publication Details
- Current genetics, v 66(3), pp 593-605
- Publisher
- Springer Nature; United States
- Grant note
- Aging Initiative / College of Medicine, Drexel University
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000515981400001
- Scopus ID
- 2-s2.0-85079176130
- Other Identifier
- 991014878410504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Genetics & Heredity