Discovery of a new DNA repair protein

DNA damage causes proteins that read genes, RNA polymerase II, to falter.

Damage to DNA prevents genes from being read. It is therefore important to repair these damages. Three proteins are known to play a role in the DNA repair process. To their surprise, scientists at Leiden University Medical Center (LUMC) found a fourth player and partially revealed how this new DNA repair protein works. The results were published in the journal Nature Cell Biology.

DNA damage causes proteins that read genes, RNA polymerase II, to falter. The crammed enzyme is recognized by other proteins, which in turn initiate DNA repair. We were already familiar with three DNA repair proteins: the Cockayne syndrome A and B proteins and the UV-sensitive syndrome protein A. Mutations in these genes cause rare congenital syndromes in patients.

in their own Publishing PhD student Yana van der Weegen and group leader Martijn Luijsterburg from the Department of Human Genetics describe a fourth protein: ELOF1. “It’s very exciting to find a new DNA repair protein,” Luijsterburg says. “We thought we all knew them now, so this was a nice surprise.”

A new DNA repair protein
“In collaboration with Rob Wolthuis’ lab in Amsterdam, we examined 20,000 human genes one by one to see which ones are involved in DNA repair,” explains Luigsterberg. “This is how we tracked down ELOF1.”

Van der Weegen and Luijsterburg discovered during their research that ELOF1 works differently from the three known proteins. “These proteins only bind to RNA polymerase II when the enzyme becomes stuck in DNA damage,” explains Van der Weegen. “ELOF1 works very differently. This protein has always been associated with RNA polymerase II and is the missing link that ensures proper pairing with other DNA repair proteins.” After the known proteins are properly coupled to RNA polymerase II, a tag is made necessary for DNA repair. “The interesting thing is that ELOF1 is exactly where the tag needs to be and it’s also essential for this to go smoothly,” says van der Weegen.

uncultivated area
There is still a lot to discover about ELOF1. “We found that ELOF1 also has a role in a second DNA repair process that we know almost nothing about,” says Luijsterburg. “This is an unexplored area and we have all the resources to work alongside Rob Wolthuis from Amsterdam UMC which is the secrets that ELOF1 wants to reveal. In short, there is still a lot to do!”

know more? Then read the entire article Nature Cell Biology