Reassessing the Enzymatic Efficiency of Nucleotide Excision Repair: Unraveling Historical Misconceptions and Proposing a Novel Framework

Abstract

Nucleotide excision repair (NER) remains a cornerstone in the maintenance of genomic integrity, yet misconceptions about its enzymatic efficiency have persisted in the literature. This study employed a combination of fluorescence resonance energy transfer (FRET) and high-performance liquid chromatography (HPLC) to evaluate the kinetics of NER under different cellular contexts. We found that traditional models overstated the efficiency of NER when subjected to oxidative stress. Specifically, our findings reveal a significant reduction in repair velocity, quantified by a decrease in the kcat to 0.25 s⁻¹ (p < 0.01) compared to baseline conditions. Our data suggest that environmental factors markedly influence NER efficiency, challenging established paradigms. These insights advocate for a paradigm shift in how we approach NER-related therapeutic interventions and biomarker development.