RECQL5 controls transcript elongation and suppresses genome instability associated with transcription stress.
RECQL5 is the sole member of the RECQ family of helicases associated with RNA polymerase II (RNAPII). We now show that RECQL5 is a general elongation factor that is important for preserving genome stability during transcription. Depletion or overexpression of RECQL5 results in corresponding shifts in the genome-wide RNAPII density profile. Elongation is particularly affected, with RECQL5 depletion causing a striking increase in the average rate, concurrent with increased stalling, pausing, arrest, and/or backtracking (transcription stress). RECQL5 therefore controls the movement of RNAPII across genes. Loss of RECQL5 also results in the loss or gain of genomic regions, with the breakpoints of lost regions located in genes and common fragile sites. The chromosomal breakpoints overlap with areas of elevated transcription stress, suggesting that RECQL5 suppresses such stress and its detrimental effects, and thereby prevents genome instability in the transcribed region of genes.
Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms, EN6 3LD, UK.
Marco
M
Saponaro
Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms, EN6 3LD, UK.
Theodoros
T
Kantidakis
Bioinformatics and Biostatistics Group, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Richard
R
Mitter
Bioinformatics and Biostatistics Group, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Gavin P
GP
Kelly
Gene Center and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
Mark
M
Heron
Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms, EN6 3LD, UK.
Hannah
H
Williams
Gene Center and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
Johannes
J
Söding
Bioinformatics and Biostatistics Group, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Aengus
A
Stewart
Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms, EN6 3LD, UK. Electronic address: Jesper.Svejstrup@cancer.org.uk.
Jesper Q
JQ
Svejstrup
D015894:Genome, Human; D042822:Genomic Instability; D057809:HEK293 Cells; D006801:Humans; D012319:RNA Polymerase II / Q000378:metabolism; D053484:RecQ Helicases / Q000378:metabolism*; D061805:Transcription Elongation, Genetic; D014158:Transcription, Genetic
C506732:RECQL5 protein, human; D012319:RNA Polymerase II; D053484:RecQ Helicases