Down Modulation of Topoisomerase I Affects DNA Repair Efficiency

DNA Repair (Amst). 2003 Oct 7;2(10):1115-26. doi: 10.1016/s1568-7864(03)00122-8.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Camptothecin / pharmacology
  • Cell Line, Tumor
  • Cell Survival / radiation effects
  • DNA Damage / radiation effects
  • DNA Repair*
  • DNA Topoisomerases, Type I / drug effects
  • DNA Topoisomerases, Type I / metabolism*
  • DNA Topoisomerases, Type I / radiation effects
  • DNA, Single-Stranded / metabolism
  • Down-Regulation
  • Humans
  • RNA, Antisense / metabolism
  • Ultraviolet Rays

Substances

  • DNA, Single-Stranded
  • RNA, Antisense
  • DNA Topoisomerases, Type I
  • Camptothecin