2015 Antineoplastics

TOPOISOMERASES
Reviewed in Molecular Biology of the Cell
This summary replicates information that you learned in the Foundations course and only includes the sections relevant to the discussion of antineoplastic drugs

Topoisomerases prevent DNA tangling

  • as a replication fork moves along double-stranded DNA, it creates a "winding problem"

  • this is solved by having topoisomerases create a swivel in the DNA helix ahead of the replication fork

  • topoisomerases are reversible nucleases that break phosphodiesterase bonds in a
    DNA strand; the bond reforms when the enzyme leaves

  • TOPOISOMERASE I produces a transient single-strand break in a manner that does not require additional energy input

  • TOPOISOMERASE II:

    • produces a transient double-strand break, and requires ATP hydrolysis

    • type II topoisomerases can separate interlocked DNA circles

    • only found in proliferating cells in eukaryotes ideal target for antineoplastic drugs
Email: Dr. Janet Fitzakerley | ©2015 University of Minnesota Medical School Duluth | Last modified: 11-apr-15 9:39 AM