Trapping of human DNA topoisomerase I by DNA structures mimicking intermediates of DNA repair.
In this report we show that human DNA Topoisomerase I (Top1) forms DNA-protein adducts with nicked and gapped DNA structures lacking a conventional Top1 cleavage site. The radioactively labeled crosslinking products were identified by SDS-gel electrophoresis. The chemical structure of the groups at 5' or 3' end of the nick does not have an effect on the formation of these covalent adducts. Therefore, all kinds of nicks, either directly induced by ionizing radiation or reactive oxygen species or indirectly induced in the course of base excision repair (BER) are targets for Top1 that competes with BER proteins and other nick-sensors. Top1-DNA covalent adducts formed in cells exposed to DNA damaging agents can promote genetic instability.
Lebedeva
Natalia
N
Institute of Chemical Biology and Fundamental Medicine, Prospect Lavrentieva 8, 630090, Novosibirsk, Russia.
Rechkunova
Nadejda
N
Boiteux
Serge
S
Lavrik
Olga
O
D003432:Cross-Linking Reagents / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D018736:DNA Adducts / Q000302:isolation & purification*; D053904:DNA Breaks, Single-Stranded; D004260:DNA Repair; D004264:DNA Topoisomerases, Type I / Q000302:isolation & purification*; D006801:Humans
D003432:Cross-Linking Reagents; D018736:DNA Adducts; D004247:DNA; D004264:DNA Topoisomerases, Type I