DNA repair scheme gets closer look for cancer therapy
The structure of DNA polymerase theta, which serves to fix double-strand breaks in DNA (at top) by bridging the hanging single-stranded ends and catalyzing DNA synthesis across the break. Researchers from Rice University and St. Jude Children’s Research Hospital in Memphis, Tennessee, studied the enzyme’s role in a process known as microhomology-mediated end joining and discovered it could be a promising target for precision cancer therapy. Credit: Illustration by Chuxuan Li/Gao Lab

Researchers from Rice University and St. Jude Children's Research Hospital have taken a close look at one of the ways cells repair broken strands of DNA and discovered details that could help make a particular enzyme a promising target for precision cancer therapy

The job of Pol theta is similar to patching a tire, it involves fixing double-strand breaks in DNA and catalyzing DNA synthesis across the break.

The processes that repair double-strand breaks are Homologous Recombination and Non-homologous End joining.

MMEJ requires Pol theta to fix a double strand.

The structural basis of Pol theta-mediated MMEJ was revealed for the first time in a study by Rice and St. Jude's.

The Rice and St. Jude researchers led the study.

DNA repair scheme gets closer look for cancer therapy
Rice University bioscientists Yang Gao and Chuxuan Li. Credit: Gustavo Raskosky/Rice University

"When DNA breaks, it's very dangerous for the cell, which has to fix it right away," said a Cancer Prevention and Research Institute of Texas Scholar in Cancer Research who studies the mechanisms of DNA replication. Cells don't want to die, and one break can kill them.

He said that one of the most usual scenarios is when a patient has a genetic abnormality. The genes can cause breast cancer if they are healthy. The genes can't be repaired through the homologous recombination pathway when there is a problem with them. The other pathways are where they have to travel.

When Pol theta is knocked out in normal cells, it won't be a problem. These deficiencies can be lethal if the knockout of thisProtein is in cells with the wrong genes. This is a very promising drug target. Only cancer cells would be hurt by a Pol theta inhibition.

Clinical trials of such treatments are being done by other labs, but the Rice lab's research adds details about the mechanism.

The work on the human version of the Asian sea bass is still being done by Li.

She loved the project. I think there's a lot that can be done to make this enzyme better. I believe there will be more people interested in this particularprotein.

The paper is co-authored by a graduate student and undergraduate from Rice and a senior scientist from St Jude.

More information is available from Chuxuan Li et al. There is a book titled "10093/nar/gkac 1201".

Journal information: Nucleic Acids Research