RECQ-like helicases Sgs1 and BLM regulate R-loop-associated genome instability.
Sgs1, the orthologue of human Bloom's syndrome helicase BLM, is a yeast DNA helicase functioning in DNA replication and repair. We show thatSGS1loss increases R-loop accumulation and sensitizes cells to transcription-replication collisions. Yeast lackingSGS1accumulate R-loops and γ-H2A at sites of Sgs1 binding, replication pausing regions, and long genes. The mutation ... signature ofsgs1Δ reveals copy number changes flanked by repetitive regions with high R-loop-forming potential. Analysis of BLM in Bloom's syndrome fibroblasts or by depletion of BLM from human cancer cells confirms a role for Sgs1/BLM in suppressing R-loop-associated genome instability across species. In support of a potential direct effect, BLM is found physically proximal to DNA:RNA hybrids in human cells, and can efficiently unwind R-loops in vitro. Together, our data describe a conserved role for Sgs1/BLM in R-loop suppression and support an increasingly broad view of DNA repair and replication fork stabilizing proteins as modulators of R-loop-mediated genome instability.
Mesh Terms:
Bloom Syndrome, Cell Line, Transformed, Cell Line, Tumor, DNA, DNA Repair, DNA Replication, Fibroblasts, Gene Dosage, Gene Expression Regulation, Genomic Instability, Histones, Humans, Nucleic Acid Conformation, Protein Binding, RNA, RecQ Helicases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Bloom Syndrome, Cell Line, Transformed, Cell Line, Tumor, DNA, DNA Repair, DNA Replication, Fibroblasts, Gene Dosage, Gene Expression Regulation, Genomic Instability, Histones, Humans, Nucleic Acid Conformation, Protein Binding, RNA, RecQ Helicases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
J. Cell Biol.
Date: Dec. 04, 2016
PubMed ID: 29042409
View in: Pubmed Google Scholar
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