Wenjian Gan Lab - R-loop-mediated genomic instability is caused by

Journal article

W. Gan, Zhishuang Guan, Jie Liu, T. Gui, K. Shen, J. Manley, Xialu Li
Genes & Development, 2011

Cite

APA Click to copy
Gan, W., Guan, Z., Liu, J., Gui, T., Shen, K., Manley, J., & Li, X. (2011). R-loop-mediated genomic instability is caused by impairment of replication fork progression. Genes &Amp; Development.

Chicago/Turabian Click to copy
Gan, W., Zhishuang Guan, Jie Liu, T. Gui, K. Shen, J. Manley, and Xialu Li. “R-Loop-Mediated Genomic Instability Is Caused by Impairment of Replication Fork Progression.” Genes & Development (2011).

MLA Click to copy
Gan, W., et al. “R-Loop-Mediated Genomic Instability Is Caused by Impairment of Replication Fork Progression.” Genes &Amp; Development, 2011.

BibTeX Click to copy

@article{w2011a,
  title = {R-loop-mediated genomic instability is caused by impairment of replication fork progression.},
  year = {2011},
  journal = {Genes & Development},
  author = {Gan, W. and Guan, Zhishuang and Liu, Jie and Gui, T. and Shen, K. and Manley, J. and Li, Xialu}
}

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.