When DNA Topology Turns Deadly – RNA Polymerases Dig in Their R-Loops to Stand Their Ground: New Positive and Negative (Super)Twists in the Replication–Transcription Conflict

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Abstract

Head-on replication–transcription conflict is especially bitter in bacterial chromosomes, explaining why actively transcribed genes are always co-oriented with replication. The mechanism of this conflict remains unclear, besides the anticipated accumulation of positive supercoils between head-on-conflicting polymerases. Unexpectedly, experiments in bacterial and human cells reveal that head-on replication–transcription conflict induces R-loops, indicating hypernegative supercoiling [(−)sc] in the region – precisely the opposite of that assumed. Further, as a result of these R-loops, both replication and transcription in the affected region permanently stall, so the failure of R-loop removal in RNase H-deficient bacteria becomes lethal. How hyper(−)sc emerges in the middle of a positively supercoiled chromosomal domain is a mystery that requires rethinking of topoisomerase action around polymerases.

Original languageEnglish (US)
Pages (from-to)111-120
Number of pages10
JournalTrends in Genetics
Volume34
Issue number2
DOIs
StatePublished - Feb 2018

Keywords

  • R-loops
  • RNase H
  • replication–transcription conflicts
  • supercoiling
  • topoisomerases

ASJC Scopus subject areas

  • Genetics

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