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

Roy, Shamayita; Adhikary, Hemanta; Isler, Sarah; D'Amours, Damien

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.

CHROMOSOME structure; EUKARYOTIC genomes; MULTIENZYME complexes; GENETIC transcription; CHROMOSOMES

eLife, 2024, p1

2050-084X

Academic Journal

10.7554/eLife.96626