Scientists have discovered a new role for a protein that may put
the brakes on cancer by stopping DNA from snapping, according to a
new study.
The protein called 'RECQL5' acts like a brake by attaching to
another important protein called RNA polymerase II - which makes
new proteins from our genes - and slows it down so it runs more
smoothly, and does not stop and 'crash' while travelling along DNA.
The scientists, at Cancer Research UK's London Research
Institute (LRI; now part of the Francis Crick Institute), found
that if RNA polymerase stops, this can lead to catastrophic
collisions with another protein known as DNA polymerase.
When these molecular machines collide on a long gene, like a
stationary car being hit by an oncoming lorry on a fast road, this
event can cause catastrophic damage to the DNA - breaking it, which
may eventually lead to the cell becoming cancerous.
The RECQL5 protein helps prevent such collisions and reduces the
likelihood that these potentially cancer-causing events occur.
Dr Jesper Svejstrup of LRI said: "We've known for some time that
cells that have lost the protein RECQL5 are more likely to become
cancerous, but until now, we've not been sure why this is.
"Our latest study shows that RECQL5 plays a vital role in
moderating RNA polymerase II speed and ensuring stable progress
across genes, which appears to reduce the number of collisions it
makes with oncoming DNA polymerase proteins on long genes.
"Knowing more about this weakness in some cells could open up
exciting new possibilities for targeting cancers with this
mistake."
RECQL5 belongs to a family of five proteins known as RecQ
helicases, three of which are linked to rare genetic diseases that
predispose a person to developing cancer.
Nell Barrie, Cancer Research UK's senior science communications
manager, said: "Discovering more about the nuts and bolts of what
causes cancer will speed up the development of better treatments
and improve our understanding of peoples' risk of developing the
disease."
The paper, RECQL5
controls transcript elongation and suppresses genome instability
associated with transcription, is published inCell.