Down modulation of topoisomerase I affects DNA repair efficiency.
Topoisomerase I (topo I) relaxes supercoiled DNA through a breakage/rejoining reaction which involves a transient covalent bond between topo I and the 3' end of the cleaved DNA strand. Topo I activity is now shown to be involved in DNA damage/repair pathway in vivo. Down regulating topo I levels using anti-sense RNA approach inhibits repair of UV-induced DNA lesions, negatively affects clonogenic survival following UV-irradiation, and reduces the formation of repair patches at the cytological level. Finally, topo I is actively recruited onto genomic DNA following DNA damage by UV light without inducing ubiquitin-dependent degradation of topo I. Thus, topo I activity is important, possibly required, for pre- or post-DNA damage processing in nucleotide excision repair (NER).
D002166:Camptothecin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair; D004264:DNA Topoisomerases, Type I / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D004277:DNA, Single-Stranded / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D016372:RNA, Antisense / Q000378:metabolism; D014466:Ultraviolet Rays
D004277:DNA, Single-Stranded; D016372:RNA, Antisense; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin