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NIH Research Festival

September 23 – 25, 2024

Whole Genome Study of Nucleotide Excision Repair and Translesion Synthesis in Saccharomyces cerevisiae

Authors

  • M Monsur
  • SA Lujan
  • AB Burkholder
  • TA Kunkel

Abstract

Cells employ diverse pathways for DNA lesion repair, and in the absence of repair, they resort to damage tolerance mechanisms. To investigate this interplay, we manipulated DNA Polymerase (Pol) ζ and Nucleotide Excision Repair (NER) Factor 1 (NEF1). Pol ζ, specialized for translesion DNA synthesis, has a catalytic subunit encoded by REV3, while NEF1 features an essential subunit encoded by RAD14. Previous studies using in vitro methods and yeast reporter genes, revealed distinct mutation patterns when altering these components. Expanding to all genomic contexts, we performed mutation accumulation experiments in Saccharomyces cerevisiae strains with a mutator variant of Pol ζ (rev3-L979F) and/or
lacking RAD14 (rad14Δ). Unlike mutation rates due to defects in DNA Mismatch Repair or replicative polymerases, rev3-L979F and rad14Δ alter mutation rates uniformly, independent of replication timing, nucleosome occupancy, or coding status. Compared to wild type yeast, RAD14 deletion increased base substitutions independent of REV3 status, suggesting that some errors repaired by NER are intractable to Pol ζ. Contrariwise, complex mutation rates increased upon RAD14 deletion and with strong synergy in the double mutant. This suggests a critical interdependence between Pol ζ translesion synthesis and NER. More study is needed to show which lesions use each pathway.

Scientific Focus Area: Molecular Biology and Biochemistry

This page was last updated on Tuesday, August 6, 2024

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Current Research Festival

  • 2025
    • Posters Session
    • General Schedule of Events
  • 2024
    • General Schedule of Events
    • 2024 NIH Distinguished Scholars Program
    • Poster Sessions
    • Concurrent Workshops
    • NIH Resource Information Fair
    • National Academy of Science Mini-Symposium
    • Special Wednesday Events
    • Vendor Exhibit Information
    • Green Labs Fair
    • Research Festival Committee
  • 2023
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    • NIH Early–Career Investigator Lectures
    • Poster Sessions
    • Concurrent Workshops
    • NIH Resource Information Fair
    • Vendor Exhibit Information
    • Research Festival Committee
  • 2021
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    • Data Blitz
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  • 2018
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