Oxidative stress triggers the preferential assembly of base excision repair complexes on open chromatin regions.
How DNA repair machineries detect and access, within the context of chromatin, lesions inducing little or no distortion of the DNA structure is a poorly understood process. Removal of oxidized bases is initiated by a DNA glycosylase that recognises and excises the damaged base, initiating the base excision repair (BER) pathway. We show that upon induction of 8-oxoguanine, a mutagenic product of guanine oxidation, the mammalian 8-oxoguanine DNA glycosylase OGG1 is recruited together with other proteins involved in BER to euchromatin regions rich in RNA and RNA polymerase II and completely excluded from heterochromatin. The underlying mechanism does not require direct interaction of the protein with the oxidized base, however, the release of the protein from the chromatin fraction requires completion of repair. Inducing chromatin compaction by sucrose results in a complete but reversible inhibition of the in vivo repair of 8-oxoguanine. We conclude that after induction of oxidative DNA damage, the DNA glycosylase is actively recruited to regions of open chromatin allowing the access of the BER machinery to the lesions, suggesting preferential repair of active chromosome regions.
Amouroux
Rachel
R
CEA, Institut de Radiobiologie Cellulaire et Moléculaire, 18 route du Panorama, UMR217 F-92265 Fontenay aux Roses, France.
Campalans
Anna
A
Epe
Bernd
B
Radicella
J Pablo
JP
D001959:Bromates / Q000633:toxicity; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000201:enzymology; D004249:DNA Damage; D045647:DNA Glycosylases / Q000032:analysis / Q000378:metabolism*; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D022041:Euchromatin / Q000737:chemistry / Q000201:enzymology*; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress; D000076105:X-ray Repair Cross Complementing Protein 1
D001959:Bromates; D002843:Chromatin; D004268:DNA-Binding Proteins; D022041:Euchromatin; D000076105:X-ray Repair Cross Complementing Protein 1; C019536:potassium bromate; D006151:Guanosine; C046215:8-hydroxyguanosine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase