Sae2/CtIP prevents R-loop accumulation in eukaryotic cells
- The University of Texas at Austin, United States
- National Institutes of Health, United States
- University of Arkansas for Medical Sciences, United States
Abstract
The Sae2/CtIP protein is required for efficient processing of DNA double-strand breaks that initiate homologous recombination in eukaryotic cells. Sae2/CtIP is also important for survival of single-stranded Top1-induced lesions and CtIP is known to associate directly with transcription-associated complexes in mammalian cells. Here we investigate the role of Sae2/CtIP at single-strand lesions in budding yeast and in human cells and find that depletion of Sae2/CtIP promotes the accumulation of stalled RNA polymerase and RNA-DNA hybrids at sites of highly expressed genes. Overexpression of the RNA-DNA helicase Senataxin suppresses DNA damage sensitivity and R-loop accumulation in Sae2/CtIP-deficient cells, and a catalytic mutant of CtIP fails to complement this sensitivity, indicating a role for CtIP nuclease activity in the repair process. Based on this evidence, we propose that R-loop processing by 5' flap endonucleases is a necessary step in the stabilization and removal of nascent R-loop initiating structures in eukaryotic cells.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Sequencing data has been deposited in GEO (accession number GSE122782).
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Sequencing data from Sae2/CtIP prevents R-loop accumulation in eukaryotic cellsNCBI Gene Expression Omnibus, GSE122782.
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Sucheta Arora
- Qiong Fu
- Xuemei Wen
- Ji-Hoon Lee
- Chung-Hsuan Kao
- Tanya T Paull
Cancer Prevention and Research Institute of Texas
- Nodar Makharashvili
- Yizhi Yin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Sae2/CtIP prevents R-loop accumulation in eukaryotic cells
eLife 7:e42733.
https://doi.org/10.7554/eLife.42733
