title: R-loop-mediated genomic instability is caused by impairment of replication fork progression.
abstract: Transcriptional R loops are anomalous RNA:DNA hybrids that have been detected in organisms from bacteria to humans. These structures have been shown in eukaryotes to result in DNA damage and rearrangements; however, the mechanisms underlying these effects have remained largely unknown. To investigate this, we first show that R-loop formation induces chromosomal DNA rearrangements and recombination in Escherichia coli, just as it does in eukaryotes. More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stability. Strikingly, we found that attenuation of replication strongly suppresses R-loop-mediated DNA rearrangements in both E. coli and HeLa cells. Our findings thus provide a direct demonstration that R-loop formation impairs DNA replication and that this is responsible for the deleterious effects of R loops on genome stability from bacteria to humans.
authors: College of Life Sciences, Peking University, Beijing 100871, China.
authors: Wenjian
authors: W
authors: Gan
authors: Zhishuang
authors: Z
authors: Guan
authors: Jie
authors: J
authors: Liu
authors: Ting
authors: T
authors: Gui
authors: Keng
authors: K
authors: Shen
authors: James L
authors: JL
authors: Manley
authors: Xialu
authors: X
authors: Li
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry; D004249:DNA Damage / Q000235:genetics; D004261:DNA Replication / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D015321:Gene Rearrangement / Q000235:genetics; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009690:Nucleic Acid Conformation; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016914:Ribonuclease H / Q000378:metabolism; D013014:SOS Response, Genetics / Q000235:genetics; D000068103:Serine-Arginine Splicing Factors
chemical_list: D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors; D004247:DNA; D016914:Ribonuclease H