Time-resolved crystallography captures light-driven DNA repair - Groupe Dynamique et Cinétique des processus moléculaires / Dynamics and Kinetics of Molecular Processes Group (IBS-DYNAMOP)
Article Dans Une Revue Science Année : 2023

Time-resolved crystallography captures light-driven DNA repair

Diogo Melo
  • Fonction : Auteur
Matthias Ruppert
Alisia Fadini
Janina Sprenger
Patrick Reinke
Viviane Kremling
Esther Lange
Robin Schubert
Elke de Zitter
Ajda Kunavar
Emma Beale
John Beale
Claudio Cirelli
Philip Johnson
Florian Dworkowski
Dmitry Ozerov
Quentin Bertrand
Maximilian Wranik
Camila Bacellar
Saša Bajt
Soichi Wakatsuki
Jonas Sellberg
Nils Huse
Dušan Turk
Henry Chapman
Thomas Lane

Résumé

Photolyase is an enzyme that uses light to catalyze DNA repair. To capture the reaction intermediates involved in the enzyme’s catalytic cycle, we conducted a time-resolved crystallography experiment. We found that photolyase traps the excited state of the active cofactor, flavin adenine dinucleotide (FAD), in a highly bent geometry. This excited state performs electron transfer to damaged DNA, inducing repair. We show that the repair reaction, which involves the lysis of two covalent bonds, occurs through a single-bond intermediate. The transformation of the substrate into product crowds the active site and disrupts hydrogen bonds with the enzyme, resulting in stepwise product release, with the 3′ thymine ejected first, followed by the 5′ base.
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Dates et versions

hal-04717786 , version 1 (18-10-2024)

Identifiants

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Nina-Eleni Christou, Virginia Apostolopoulou, Diogo Melo, Matthias Ruppert, Alisia Fadini, et al.. Time-resolved crystallography captures light-driven DNA repair. Science, 2023, 382 (6674), pp.1015-1020. ⟨10.1126/science.adj4270⟩. ⟨hal-04717786⟩
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