The Smc5/6 Complex Counteracts R-loop Formation at Highly Transcribed Genes in Cooperation with RNase H2

Overview

Journal Elife

Specialty Biology

Date 2024 Oct 15

PMID 39404251

Authors

Shamayita Roy

Hemanta Adhikary

Sarah Isler

Damien DAmours

Affiliations

Soon will be listed here.

Abstract

The R-loop is a common transcriptional by-product that consists of an RNA-DNA duplex joined to a displaced strand of genomic DNA. While the effects of R-loops on health and disease are well established, there is still an incomplete understanding of the cellular processes responsible for their removal from eukaryotic genomes. Here, we show that a core regulator of chromosome architecture -the Smc5/6 complex- plays a crucial role in the removal of R-loop structures formed during gene transcription. Consistent with this, budding yeast mutants defective in the Smc5/6 complex and enzymes involved in R-loop resolution show strong synthetic interactions and accumulate high levels of RNA-DNA hybrid structures in their chromosomes. Importantly, we demonstrate that the Smc5/6 complex acts on specific types of RNA-DNA hybrid structures in vivo and promotes R-loop degradation by the RNase H2 enzyme in vitro. Collectively, our results reveal a crucial role for the Smc5/6 complex in the removal of toxic R-loops formed at highly transcribed genes and telomeres.

Citing Articles

The Smc5/6 complex counteracts R-loop formation at highly transcribed genes in cooperation with RNase H2.

Roy S, Adhikary H, Isler S, DAmours D Elife. 2024; 13.

PMID: 39404251 PMC: 11620742. DOI: 10.7554/eLife.96626.

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