March 14, 2019

Correctly copying DNA

A precise understanding of how the enzyme topoisomerase II cuts DNA could lead to better anti-cancer therapies.

The enzyme topoisomerase II resolves topological roadblocks that form during the copying and expression of genetic material by generating double-stranded breaks in one DNA segment, transporting another DNA segment through the break, and rejoining the two ends.

Tight regulation of the DNA breakage/rejoining cycle of topoisomerase II is very important to cell survival. Furthermore, several anticancer drugs exploit this DNA cleavage reaction to kill cancerous cells.

Previous studies have demonstrated that the ability to bend the double helix at specific sites is critical for topoisomerase II to cleave DNA.

Now in a study published in the journal Cell Chemical Biology, Neil Osheroff, PhD, and collaborators in South Korea used single-molecule fluorescence to monitor the individual reaction steps mediated by topoisomerase II.

Their observations suggest that the enzyme induces sequence-preferential bending by active protein-DNA interactions. Thus, the cleavage site of topoisomerase II is determined during the DNA bending step and is not an intrinsic property of the DNA.

This research was supported in part by grants from the National Institutes of Health (GM033944, GM126363).