The other function of DNA photolyase: stimulation of excision repair of chemical damage to DNA.
DNA photolyase is a light-dependent DNA repair enzyme. It binds to cyclobutane pyrimidine dimers <PyrPyr> in DNA and upon excitation with a blue light photon splits the cyclobutane ring and restores the pyrimidines to native forms. The enzyme is specific for pyrimidine dimers, and it is not known to catalyze any other reaction either in ground or in excited state. However, when photolyase binds to <PyrPyr> but cannot catalyze repair because of lack of photoreactivating light, it still aids DNA repair by stimulating the nucleotide excision repair system. Recently, it was found that yeast photolyase binds to other lesions in DNA. In particular, the binding to cisplatin damaged DNA was highly specific. However, in vivo experiments revealed that this binding, in contrast to <PyrPyr> binding, did not stimulate but actually inhibited the removal of cisplatin damage by excision repair and hence photolyase sensitized cells to killing by cisplatin. In the present study, it is demonstrated that Escherichia coli DNA photolyase binds specifically to cisplatin 1,2-d(GpG) intrastrand cross-link and stimulates the removal of the lesion by E. coli excision nuclease in vitro. In agreement with the in vitro data, in vivo experiments revealed that photolyase makes cells more resistant to cisplatin killing.
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599, USA.
Z
Z
Ozer
J T
JT
Reardon
D S
DS
Hsu
K
K
Malhotra
A
A
Sancar
D001665:Binding Sites; D002945:Cisplatin / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000378:metabolism*; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D007700:Kinetics; D017785:Photons; D011485:Protein Binding; D011740:Pyrimidine Dimers / Q000378:metabolism; D013379:Substrate Specificity
D011740:Pyrimidine Dimers; D004247:DNA; D004255:Deoxyribodipyrimidine Photo-Lyase; D002945:Cisplatin