Molecular movie of DNA repair by a photolyase

Photolyase is an enzyme harnessing visible light to repair a DNA strand that has been damaged by UV light. In a study published in Science, researchers have used X-rays from free electron lasers to reveal the atomic details of the molecular repair mechanism of a damaged DNA strand. To do this, they have used time-resolved crystallography on a time scale from hundreds of picoseconds to hundreds of microseconds.

Antoine Royant and Sylvain Engilberge, from the Synchrotron group of the IBS, together with Nicolas Caramello, from the Structural Biology group of the ESRF, have spectroscopically characterized at the icOS Lab the crystals used at XFELs, contributed to the preparation of samples in anaerobic conditions under red light during the diffraction experiments, then developed a global analysis of difference electron density maps in order to provide a robust model of the succession of the various steps in the repair mechanism.

The accumulated data, recorded at two XFELs in various experimental sessions, constitutes a genuine molecular movie of the complete sequence of events in photolyase-catalyzed DNA repair, from the absorption of a light photon by the flavin cofactor to the dissociation of the protein/DNA complex.

Visualizing the DNA repair process by a photolyase at atomic resolution. Maestre-Reyna M, Wang PH, Nango E, Hosokawa Y, Saft M, Furrer A, Yang CH, Putu EPGN, Wu WJ, Emmerich HJ, Caramello N, Franz-Badur S, Yang C, Engilberge S, Wranik M, Glover HL, Weinert T, Wu HY, Lee CC, Huang WC, Huang KF, Chang YK, Liao JH, Weng JH, Gad W, Chang CW, Pang AH, Yang KC, Lin WT, Chang YC, Gashi D, Beale E, Ozerov D, Nass K, Knopp G, Johnson PJM, Cirelli C, Milne C, Bacellar C, Sugahara M, Owada S, Joti Y, Yamashita A, Tanaka R, Tanaka T, Luo F, Tono K, Zarzycka W, Müller P, Alahmad MA, Bezold F, Fuchs V, Gnau P, Kiontke S, Korf L, Reithofer V, Rosner CJ, Seiler EM, Watad M, Werel L, Spadaccini R, Yamamoto J, Iwata S, Zhong D, Standfuss J, Royant A, Bessho Y, Essen LO, Tsai MD. Science 2023, 382:eadd7795.

Contact : Antoine Royant (IBS/Synchrotron Group)