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
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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
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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
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TOPOISOMERASE II:
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produces a transient double-strand break, and requires ATP hydrolysis
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type II topoisomerases can separate interlocked DNA circles
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- only found in proliferating cells in eukaryotes è ideal target for antineoplastic drugs