DNA lesion recognition and repair mechanism by photolyase and DNA glycosylase
Choi, Monica Sunok
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DNA is constantly bombarded by endogenous reagents threatening their viability and genomic stability. The resulting products cause DNA lesions causing serious implications on cell health and mutagenesis. Recent biochemical assays allow the detection of various types of lesions, notably high performance liquid chromatography (HPLC) and mass spectrometry. Structural and biochemical studies have provided insight into DNA damage recognition and repair mechanisms. Research indicates both photolyase and DNA glycosylase have multiple interactions with the DNA phosphodeoxyribose backbone and perform lesion repair by base- flipping out of the helix and insertion into the enzyme pocket. Photolyase crystal structure strongly supports the electron transfer take place over van der Waals distance between the flavin and the lesion. Concerted efforts have suggested Uracil- DNA glycosylase recognize uracil through a “Serine- Proline pinch” mechanism and repair occurs through flipping the nucleotide into the enzyme active site.