Scientists untangle DNA repair web

In collaboration with the Press Association

US scientists have begun to untangle the complex way that cells respond to DNA damage after exposure to toxic substances.

The results of their research were published today in the journal Science.

Previous work has identified the individual components of this response, but this is the first time they have been analysed as a complete system.

The researcher, a collaborative study led by scientists at the University of California, San Diego, said that the information would lead to a better understanding of many human diseases, including cancer, and may one day lead to new treatments.

"DNA damage is a basic physiological process that is important to coping with environmental toxins and a number of congenital diseases," said lead author professor Trey Ideker.

"Over the past several decades, scientists have discovered many parts of the DNA-damage-repair machinery.

"But what has been missing until now is a 'systems biology' approach that explains how all the parts function together to enable a cell to repair its DNA while under routine assault."

To study the phenomenon, researchers exposed yeast cells to methyl methanesulphonate (MMS), a substance known to have similar carcinogenic properties to tobacco smoke.

The team uncovered a network of 30 different inter-related proteins, called transcription factors, which interacted with more than 5,000 yeast genes in response to the DNA damage caused by MMS exposure.

Many of the proteins and genes already had established roles in DNA repair, but others had more diverse functions such as regulation of cell division and metabolism.

The researchers speculate that cells make use of the necessary pause in growth while DNA is being repaired to carry out a number of ?housekeeping? functions.

"It's almost as if cells have something akin to a computer program that becomes activated by DNA damage, and that program enables the cells to respond very quickly," said researcher Craig Mak.

"And this program is easily recognizable as operating in everything from yeasts to humans and mice to fruit flies."

"With this model now in hand, we'd like to take a much closer look at the cell's response to environmental toxins," said professor Ideker.

"What we quickly realized is that we had uncovered not just a model of DNA repair, but a blueprint of how the initial event of DNA damage is transmitted by these transcription factors to repair processes and all the other important functions of the cell. "We'd like to understand what goes wrong in certain congenital diseases involving DNA repair, and we'd also like to understand how the model plays a role in various cancers."

Find out more about DNA repair

Read the paper online