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R We There Yet? R-Loop Hazards to Finishing the Journey

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1 R We There Yet? R-Loop Hazards to Finishing the Journey
Catherine J. Potenski, Hannah L. Klein  Molecular Cell  Volume 44, Issue 6, Pages (December 2011) DOI: /j.molcel Copyright © 2011 Elsevier Inc. Terms and Conditions

2 Figure 1 Disrupted Transcription Can Lead to R-Loops
RNA polymerase (RNAP) transcribes RNA (red) from a DNA template (blue), and blocking of RNAP can lead to complex arrest, R-loop formation, and genome instability. In Prokaryotes, transcription and translation are coupled, so actively translating ribosomes immediately bind to the newly transcribed RNA (top left). When translation is perturbed, there is an increased incidence of RNAP arrest. In this case, codirectional collisions with the replisome (middle left) can lead to R-loops. In Eukaryotes, nascent transcripts are bound by splicing factors and processing factors (such as the THO/TREX complex) and are exported through the nuclear pore (top right) for translation in the cytoplasm. If any of these processing factors are impaired (middle right), the transcript is not engaged or tethered and becomes free to reanneal to the template DNA, forming an R-loop (bottom). R-loops also arise from head-on collisions between transcription and replication machines (middle), where the barrier created by a disrupted replication fork is too great to overcome. This blocks the RNA polymerase, leading to R-loop formation. The single-stranded DNA region of an R-loop is highly susceptible to breakage, leading to double strand breaks (DSBs) and chromosome instability. RNA:DNA hybrids can be eliminated from the genome though the action of RNaseH enzymes. Molecular Cell  , DOI: ( /j.molcel ) Copyright © 2011 Elsevier Inc. Terms and Conditions


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