Two distinct mechanisms of Topoisomerase 1-dependent mutagenesis in yeast.

Journal Article (Journal Article)

Topoisomerase 1 (Top1) resolves transcription-associated supercoils by generating transient single-strand breaks in DNA. Top1 activity in yeast is a major source of transcription-associated mutagenesis, generating a distinctive mutation signature characterized by deletions in short, tandem repeats. A similar signature is associated with the persistence of ribonucleoside monophosphates (rNMPs) in DNA, and it also depends on Top1 activity. There is only partial overlap, however, between Top1-dependent deletion hotspots identified in highly transcribed DNA and those associated with rNMPs, suggesting the existence of both rNMP-dependent and rNMP-independent events. Here, we present genetic studies confirming that there are two distinct types of hotspots. Data suggest a novel model in which rNMP-dependent hotspots are generated by sequential Top1 reactions and are consistent with rNMP-independent hotspots reflecting processing of a trapped Top1 cleavage complex.

Full Text

Duke Authors

Cited Authors

  • Cho, J-E; Kim, N; Li, YC; Jinks-Robertson, S

Published Date

  • March 1, 2013

Published In

Volume / Issue

  • 12 / 3

Start / End Page

  • 205 - 211

PubMed ID

  • 23305949

Pubmed Central ID

  • PMC3594648

Electronic International Standard Serial Number (EISSN)

  • 1568-7856

Digital Object Identifier (DOI)

  • 10.1016/j.dnarep.2012.12.004


  • eng

Conference Location

  • Netherlands