NSU Researchers Study How Proteins Collide with DNA

The nucleus of a human cell is a hectic place where DNA constantly interacts with many proteins. Some proteins actively move along DNA strands, others are tightly bound to specific places, and still others crash into them while moving. Researchers at the NSU Natural Sciences Department’s Laboratory of Protein Engineering studied what happens when moving DNA polymerases, the proteins that copy genetic information, collide with other proteins that are tightly attached to DNA. The results of their work were published in the Swiss journal “Genes”.

Anna Yudkina, Junior Researcher at the laboratory, explained,

We looked, generally,at what could displace proteins that sit firmly on DNA. We studied this using two DNA repair proteins, OGG1 and NEIL1, that are involved in repairing oxidized DNA, and the Cas nuclease, which is a very popular genomic editing tool. One can assume that the collision mechanism will be universal because there are a lot of proteins and they are all different. It is unlikely that each protein has its own way of disengaging from DNA.

The scientists used proteins of various origin (bacterial, viral and human)and assessed how the properties of enzymes moving along DNA affect their ability to push tightly bound obstacles off.

It turned out that DNA polymerases are capable of displacing the OGG1 and NEIL1 proteins from DNA. This increases the number of these enzymes in the free state and thus accelerates the action of the DNA repair system. The Cas9 protein is so tightly bound that no polymerase is able to knock it off. Artificial barriers for other proteins on DNA have already been made using Cas9. and the data from Siberian scientists helps to understand how these obstacles behave in human cells, and provides a key to new ways of using Cas9 to control the genome.