English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Crystal structure and mechanism of a DNA (6-4) photolyase

MPS-Authors
/persons/resource/persons92083

Barends,  Thomas
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons92561

Cryle,  Max
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons92695

Domratcheva,  Tatiana
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons95189

Schlichting,  Ilme
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Maul, M. J., Barends, T., Glas, A. F., Cryle, M., Domratcheva, T., Schneider, S., et al. (2008). Crystal structure and mechanism of a DNA (6-4) photolyase. Angewandte Chemie International Edition: a journal of the Gesellschaft Deutscher Chemiker, 47(52), 10076-10080. doi:10.1002/anie.200804268.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0028-7993-8
Abstract
UV irradiation of cells gives rise to the formation of cyclobutane pyrimidine dimers (CPD) and so-called (6-4) DNA lesions (Scheme 1). Both lesions are major photoproducts formed in dipyrimidine sequences of double-stranded DNA.1, 2 Repair of these lesions is essential because of their high mutagenic potential. Particularly important in many organisms are the photolyase-mediated repair systems that are able to split CPD lesions and (6-4) lesions directly back into their corresponding monomers.1, 2 While formation and photolyase repair of CPD lesions is well studied, little is known about (6-4) lesions. In particular, the mechanism of repair of the (6-4) lesions by (6-4) DNA photolyases is a long-standing question. Currently it is believed that the enzyme rearranges the (6-4) lesion with the help of two conserved histidine residues in the active site to form an oxetane intermediate (Scheme 1), which is split after single-electron donation from a light-activated FADH−.3, 4 We report here the first crystal structures of a (6-4) DNA photolyase enzyme. The structures show the enzyme in complex with a (6-4) lesion containing DNA before and after in situ repair. Based on the structural and biochemical data we propose a modified repair mechanism that lacks the strained oxetane intermediate.