The structures of two intermediates en route to DNA repair within a (6-4) photolyase

Dose-controlled X-ray crystallography of (6-4) photolyase from Vibrio cholerae captured 6-4PP conversion into an oxetane species and revealed a previously unanticipated hemi-cleaved intermediate.

• Why it matters: Repair of mutagenic (6-4) photoproducts requires coordinated hydroxyl transfer and interbase bond cleavage, yet the key oxetane step has not been definitively observed for decades.
• What they did: The team used dose-controlled X-ray crystallography to track the transformation of 6-4PP within the enzyme and to identify intermediate species along the reaction pathway.
• The result: The observed progression through oxetane, hemi-cleaved, and fully repaired species indicates existing (6-4) photolyase repair models need reexamination to match these structural intermediates.

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