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Abstract

Ultraviolet radiation can generate lesions in DNA in which two adjacent bases become covalently linked as a cyclobutene pyrimidine dimer. However, the enzyme that fixes these lesions also takes advantage of the energy in light to initiate the repair reaction. Two independent groups, Maestre-Reyna et al. and Christou et al., used time-resolved crystallography at an x-ray free electron laser to capture the process of DNA repair from picoseconds to microseconds (see the Perspective by Vos). A bent flavin conformation appears very early after the excitation pulse, and the enzyme constrains the cofactor conformation to favor electron transfer to the lesion rather than deexcitation. The cyclobutane dimer is cleaved one bond at a time with a transient intermediate predominating at 1 nanosecond. After cleavage, the separated bases occupy more space in the active site than in the lesion, which facilitates dissociation from the enzyme.

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