Primary Fibroblasts of Cockayne Syndrome Patients Are Defective in Cellular Repair of 8-Hydroxyguanine and 8-Hydroxyadenine Resulting From Oxidative Stress
J Tuo, Pawel Jaruga, H Rodriguez, V. Bohr, Miral M. Dizdar
Cockayne Syndrome (CS) is a genetic human disease with clinical symptoms that include neurodegeneration and premature aging. We show that primary fibroblasts from CS patients lack the ability to efficiently repair oxidative DNA damage. Primary fibroblasts of 11 CS patients and 6 control individuals were exposed to 2 Gray of ionizing radiation to induce oxidative DNA damage and then allowed to repair the damage. DNA from cells was analyzed using liquid chromatography/mass spectrometry to measure the biologically important lesions 8'-hydroxy-2'-deoxyadenosine (8-OH-dGuo) and 8'-hydroxy-2'-deoxyadenosine (8-OH-dAdo). Following radiation, no significant change in background levels of 8-OH-dGuo and 8-OH-dAdo was observed in normal human control cells, indicating complete cellular repair. In contrast, cells from CS patients accumulated significant amounts of these lesions, providing evidence for lack of DNA repair. This was supported by the observation that incision of 8-OH-dGuo- or 8-OH-dAdo-containing oligonucleotides by whole cell extracts of CS patients was deficient compared to that by whole cell extracts of normal individuals. This study suggests that a deficiency in cellular repair of oxidative DNA damage might contribute to developmental defects in CS patients.
aging, cockayne snydrome, DNA repair, mutagenesis, neurodegenerative diseases, oxidative DNA damage
, Jaruga, P.
, Rodriguez, H.
, Bohr, V.
and Dizdar, M.
Primary Fibroblasts of Cockayne Syndrome Patients Are Defective in Cellular Repair of 8-Hydroxyguanine and 8-Hydroxyadenine Resulting From Oxidative Stress, Faseb Journal
(Accessed February 21, 2024)