# Expression of human RECQL5 in Saccharomyces cerevisiae causes transcription defects and transcription-associated genome instability

## TL;DR

Expressing human RECQL5 in yeast causes transcription issues and genome instability, suggesting it interacts with RNA polymerase II.

## Contribution

Demonstrates that human RECQL5 can function in yeast and affects transcription and genome stability.

## Key findings

- RECQL5 expression in yeast leads to growth inhibition and increased genotoxic sensitivity.
- RECQL5 causes transcription termination defects and readthrough transcription at G+C-rich genes.
- RECQL5-ID mutant interacts with RNA polymerase II in cells despite reduced in vitro association.

## Abstract

RECQL5 is a member of the conserved RecQ family of DNA helicases involved in the maintenance of genome stability that is specifically found in higher eukaryotes and associates with the elongating RNA polymerase II. To expand our understanding of its function we expressed human RECQL5 in the yeast Saccharomyces cerevisiae, which does not have a RECQL5 ortholog. We found that RECQL5 expression leads to cell growth inhibition, increased genotoxic sensitivity and transcription-associated hyperrecombination. Chromatin immunoprecipitation and transcriptomic analysis of yeast cells expressing human RECQL5 shows that this is recruited to transcribed genes and although it causes only a weak impact on gene expression, in particular at G + C-rich genes, it leads to a transcription termination defect detected as readthrough transcription. The data indicate that the interaction between RNAPII and RECQL5 is conserved from yeast to humans. Unexpectedly, however, the RECQL5-ID mutant, previously shown to have reduced the association with RNAPII in vitro, associates with the transcribing polymerase in cells. As a result, expression of RECQL5-ID leads to similar although weaker phenotypes than wild-type RECQL5 that could be transcription-mediated. Altogether, the data suggests that RECQL5 has the intrinsic ability to function in transcription-dependent and independent genome dynamics in S. cerevisiae.

The online version contains supplementary material available at 10.1007/s00438-024-02152-3.