Unjamming the Genome After DNA Damage: A Gene Regulatory Multi-Tool Has Yet Another Function

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A protein complex that is involved in nearly every step in the regulatory control of gene expression in cells has now been shown also to play a key role in clearing potential traffic jams in the production of RNA.

A protein complex that is involved in nearly every step in the regulatory control of gene expression in cells has now been shown also to play a key role in clearing potential traffic jams in the production of RNA.

RNA polymerase II (RNAPII)—the enzyme that produces RNA from a DNA template—can become stuck due to damage to the DNA template, and these jams must be cleared to restore gene expression and normal cell function. New research shows that the master regulatory complex, “Ccr4-Not,” performs this task, associating with RNAPII during the transcription of RNA from DNA and marking RNAPII for degradation when it becomes stuck, allowing the DNA to be repaired and normal cell function to resume.

A paper describing the research by Penn State scientists appears online in the journal Genes & Development on April 4, 2019.

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Image: Ccr4-Not to the rescue. A) Ccr4-Not complex associates with RNA polymerase II (RNAPII) as it travels along a strand of DNA producing RNA. B) When RNAPII becomes stuck due to DNA damage, Ccr4-Not recruits factors that mark RNAPII with a small signaling molecule called ubiquitin. C) Ubiquitylation triggers degradation of RNAPII, allowing DNA repair enzymes to repair the damage and restore gene expression.  Credit: Reese Laboratory, Penn State.