Study reveals unknown role of RNA in DNA damage repair

A multi-institutional team of researchers led by Georgia Tech’s Francesca Storrisi has discovered a previously unknown role for RNA. Their insights could transform our understanding of genetic health and evolution, as well as lead to improved treatments for diseases such as cancer and neurodegenerative diseases.

RNA molecules are best known as protein-producing messengers. They carry genetic instructions from DNA to ribosomes, factories in cells that turn amino acids into proteins needed for many cellular functions. But Storici’s team has discovered that RNA also helps cells repair severe DNA damage called double-strand breaks (DSBs).

A DSB means that both strands of the DNA helix are broken. Cells have the tools to repair, but DSBs are significant damage that, if not properly repaired, can lead to mutations, cell death, or cancer. (Interestingly, cancer treatments such as chemotherapy and radiation therapy can cause DSB.)

Storisi, a professor in the School of Biological Sciences, has dedicated his research to studying the molecules and mechanisms underlying damaged DNA repair. Ten years ago, she and her collaborators discovered that RNA could serve as a template for DSB repair and published their findings in Nature.

“We found that RNA can directly promote DSB repair mechanisms,” said Storisi, whose lab collaborated with math experts from Natasha Jonoska’s lab at the University of South Florida. All are part of the Southeast Center for Mathematics and Biology, based at Georgia Tech. They describe their findings in the journal Nature Communications.

“These findings provide new understanding of the potential role of RNA in maintaining genome integrity and driving evolutionary change,” Storici added.

The researchers visualized millions of DSB repair events using variation distance graphs, providing a comprehensive snapshot of sequence variation. The graph highlights the significant differences in repair patterns depending on the location of the DSB.

This mathematical approach also revealed significant differences in repair efficiency, pointing to the potential of RNA in modulating DSB repair outcomes.

“These findings highlight the important role of mathematical visualization in understanding complex biological mechanisms and pave the way for targeted interventions in genomic stability and therapeutic research. “It’s possible,” Professor Jonoska said.

Molecule monotony

When a DSB occurs in DNA, it is like a load-bearing beam in a building failing. Careful and precise restoration is required to ensure the stability of the building (or DNA). Pieces must be recombined precisely to prevent further damage or mutations. You need a reliable foreman on site to repair damaged buildings. DSB needs something very similar.

“The key mechanism we identified is that RNA can position and hold broken DNA ends in place and facilitate the repair process,” said the researchers, who conducted research in both human and yeast cells. explained Storici of the team.

Specifically, they discovered that RNA molecules and broken parts of DNA can fit together like puzzle pieces. When RNA has this type of complementarity with a DNA cut site, it goes beyond its traditional coding function and acts as a scaffold or guide, indicating where in the cellular machinery to perform repair. Over thousands of years, cells have evolved complex mechanisms to modify DSBs, each acting like a different tool in the same toolbox.

Storici’s team showed that RNA can influence which tools are used depending on its complementarity with the broken DNA strand. This means that in addition to being an important protein-producing messenger, RNA acts as both overseer and worker when it comes to DNA repair.

A better understanding of the role of RNA in DNA repair could lead to new strategies to strengthen repair mechanisms in healthy cells and reduce the harmful effects of treatments such as chemotherapy and radiation.

“RNA has a much broader range of functions than we knew,” Storici said. “While much research is still needed into these mechanisms, this work opens new avenues to explore how RNA can be used in medicine and may lead to new treatments for cancer and other genetic diseases. may lead to.”

Storici and other researchers continue to investigate the effects of RNA in DNA repair, and their discoveries could have a lasting impact on human health and evolution. That means better gene therapies, new cancer treatments, anti-aging strategies, and the ability to influence how organisms adapt and evolve.