New understanding about DNA repair rewrites the textbooks

New knowledge about how DNA is repaired is rewriting textbooks and could improve our understanding of how to treat aging-related disease.

Associate Professor Tamas Fischer is leading a team from ANU and Heidelberg University that has discovered new factors that are essential for DNA repair.

The research group has discovered structures known as RNA-DNA hybrids that are essential for the precise repair of DNA breaks.

DNA breaks are a normal part of life and are usually repaired using precise mechanisms that return the DNA to its original state. However if the breaks are not repaired properly they can result in mutations, which are responsible for the development of cancer and aging-related diseases.

DNA, which contains our genetic blueprint, consists of two strands which form a double helix. RNA is single stranded and copies the genetic information stored in the DNA and uses it to generate proteins in the cell.

But occasionally RNA can replace one of the DNA strands, creating a hybrid structure composed of DNA and RNA, known as RNA-DNA hybrids. These hybrid structures were previously thought to harm the cell by damaging the DNA.

Fischer’s research team was surprised to discover that RNA-DNA hybrids also have a positive role in maintaining error-free DNA.

“We found that without RNA-DNA hybrids, breaks are repaired but not precisely, so the resulting DNA will most certainly contain mutations,” Associate Professor Fischer says.

“These mutations might be harmless, or might change important functions in the cell leading to diseases such as cancer and aging-related diseases.”

The researchers also discovered two enzymes, known as RNase H enzymes that target these hybrid structures and are also necessary for the repair of damaged DNA.

“These enzymes are actually found in every living cell, but until now we didn’t fully realise the extent of their function,” says Associate Professor Fisher.

“Our study has revealed that these enzymes are essential for DNA repair and this is probably one of their most important functions.”

The new understanding of RNase H enzymes could be put to good use.

Drugs might be used to improve DNA repair to prevent aging-related diseases such as cardiovascular disease, cancer or neuro-degenerative disease. Alternatively, chemotherapy drugs that block DNA repair in tumours could be developed to treat cancer.

“The better we understand these repair pathways, the greater potential we have to prevent mutations from accumulating,” says Associate Professor Fischer.

“We are now investigating whether we can inhibit the formation or the degradation of these RNA-DNA hybrids using drugs that target the RNase H enzymes, to promote the precise repair of DNA.”

Published in Research Highlights – The John Curtin School of Medical Research, ANU, May 2017.

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