Genetic investigation of formaldehyde-induced DNA damage response in Schizosaccharomyces pombe.

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ID: 98380
2020
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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.
Reference Key
anandarajan2020geneticcurrent Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Anandarajan, Vinesh;Noguchi, Chiaki;Oleksak, Julia;Grothusen, Grant;Terlecky, Daniel;Noguchi, Eishi;
Journal current genetics
Year 2020
DOI
10.1007/s00294-020-01057-z
URL
Keywords
formaldehyde DNA repair dna damage base excision repair icl nucleotide excision repair fanconi anemia crosslink dna–protein crosslink dpc environmental toxin fmd1 formaldehyde dehydrogenase interstrand crosslink ner replication fork

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