RECQL5 controls transcript elongation and suppresses genome instability associated with transcription stress
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RECQL5 controls transcript elongation and suppresses genome instability associated with transcription stress. / Saponaro, Marco; Kantidakis, Theodoros; Mitter, Richard; Kelly, Gavin P.; Heron, Mark; Williams, Hannah; Söding, Johannes; Stewart, Aengus; Svejstrup, Jesper Q.
I: Cell, Bind 157, Nr. 5, 2014, s. 1037-1049.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - RECQL5 controls transcript elongation and suppresses genome instability associated with transcription stress
AU - Saponaro, Marco
AU - Kantidakis, Theodoros
AU - Mitter, Richard
AU - Kelly, Gavin P.
AU - Heron, Mark
AU - Williams, Hannah
AU - Söding, Johannes
AU - Stewart, Aengus
AU - Svejstrup, Jesper Q.
N1 - Funding Information: This work was supported by grants from Association for International Cancer Research, the European Research Council, and Cancer Research UK (to J.Q.S.). We thank Nick Matthews and staff in the Advanced Sequencing Facility for their contribution; the Cell Services facility for assistance with cell lines; and members of the Svejstrup laboratory for comments on the manuscript.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
U2 - 10.1016/j.cell.2014.03.048
DO - 10.1016/j.cell.2014.03.048
M3 - Journal article
C2 - 24836610
AN - SCOPUS:84901408644
VL - 157
SP - 1037
EP - 1049
JO - Cell
JF - Cell
SN - 0092-8674
IS - 5
ER -
ID: 330898891