Jumping repair proteins fix DNA ‘potholes’

New research by British and US scientists has seen repair proteins appear to jump between DNA molecules and sliding across strands to fix mistakes, like ‘jumping fleas’.

Boffins at the University of Essex in the UK as well as Pittsburgh and Vermont in the US discovered this tagging proteins with quantum dots, reporting the findings in Molecular Cell.

The aim of the research was to discover how a repair system worked rapidly to maintain the integrity of DNA code sequences, which were constantly being bombarded with environmental toxins.

Bennett Van Houten, professor of pharmacology and chemical biology at the University of Pittsburgh, said that the way the repair system worked was an important unanswered question in the field.

He said: “It has to be able to identify very small mistakes in a three-dimensional morass of gene strands. It is akin to spotting potholes on every street all over the country and getting them fixed before the next rush hour.”

Two repair proteins (UvrA and UvrB) were tagged with quantum dots, which are semiconductor nanocrystals that light up in different colours. The clumped DNA was also stretched into ‘tightropes’ to see the process clearly.

UvrA proteins jumped from one DNA molecule to the next, staying for about seven seconds before going on to the next one.

But when a UvrA molecule formed a complex with two UvrB molecules (UvrAB), this searched more efficiently by sliding along the DNA for as long as 40 seconds before jumping to another molecule.

As well as jumping and sliding, there were also periods of ‘paused motion’ where UvrAB moved slower and purposely.

 “Paused motion could represent UvrAB complexes checking for structural abnormalities associated with DNA damage,” said co-author David Warshaw, professor at the University of Vermont.

The long-term question would be how and why the repair proteins conducted the repairs, perhaps by sampling the shape and configuration of the DNA by interacting with it. Could errors alter the DNA structure, triggering a corrective response of the proteins?