PerspectiveMolecular Biology

A New Twist for Topoisomerase

Science  24 Jun 2011:
Vol. 332, Issue 6037, pp. 1510-1511
DOI: 10.1126/science.1208450

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Summary

The worlds of RNA and DNA are not entirely separate. They frequently come together when RNA/DNA hybrids form during replication and transcription, which often induces genome instability (13). An enzyme called topoisomerase (Top) plays an important role in preventing RNA/DNA annealing during transcription (1). Another enzyme, ribonuclease H (RNase H), helps maintain genome integrity by removing RNA from hybrids (2, 3). On page 1561 of this issue, Kim et al. (4) report that Top1, one of the two types of topoisomerase, not only prevents the formation of often deleterious hybrid structures called R-loops, but also participates in the removal of single ribonucleotides (rNMPs), which are incorporated during DNA replication and have escaped the repair system. Using yeast, Kim et al. also show that, when there is a rNMP at the site of Top1 cleavage, the enzyme can create irreversible breaks in the DNA strand, assaulting genome stability and perhaps contributing to disease.

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