Journal
CELL
Volume 157, Issue 5, Pages 1037-1049Publisher
CELL PRESS
DOI: 10.1016/j.cell.2014.03.048
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Funding
- Association for International Cancer Research
- European Research Council
- Cancer Research UK
- Cancer Research UK [11567] Funding Source: researchfish
- Worldwide Cancer Research [09-0730] Funding Source: researchfish
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RECQL5 is the solemember of theRECQfamily 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 thatRECQL5 suppresses such stress and its detrimental effects, and thereby prevents genome instability in the transcribed region of genes.
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