DNA insights could lead to cancer treatments

New structures within cells could help scientists understand how damage to DNA can be repaired and prevented, according to researchers at the University of Copenhagen.

In time, it is hoped that these insights could be used to develop new cancer treatments, given the disease’s link to faulty DNA replication, as well as other conditions related to the immune system.

The area of interest is the histones, which is a group of basic proteins found within the material that makes up chromosomes (chromatin). They allow for the tight packing of genetic material into a very small space that is necessary to fit an entire genome into a cell nucleus. This is no small task, as DNA strands are generally about two metres long - 10,000 times bigger than the entire cell into which they must fit.

There are five types of histones, four of which have been classified as “core”. They are placed along the DNA strands like beads on a string, and are responsible for a vast number of functions relating to the proper functioning of all types of genetic material. Some scientists have previously described them as being like balls of yarn that have tails hanging off.

It had previously been established that the “tails” of the four core histones are able to detect any damage to DNA, and then attract the necessary proteins to repair it. However, a fifth histone, H1, was until recently something of a mystery.

Now the team have been able to confirm that it also has the ability to summon repair proteins, opening up new avenues for research into a variety of serious health conditions.

Their research was based on observations that came from using a mass spectrometer and applying a technique that had been developed in collaboration with scientists at the Novo Nordisk Foundation Centre for Protein Research.

Lead researcher Niels Mailand said: "In international research, the primary focus has been on the core histones and their functionality, whereas little attention has been paid to the H1 histone, simply because we weren't aware that it too influenced the repair process. Having discovered this function in the H1 constitutes an important piece of the puzzle of how cells protect their DNA, and it opens a door onto hitherto unknown and highly interesting territory."

“The knowledge we generate can prove important to the development of more targeted treatments for diseases caused by cellular changes, including cancer. By mapping the function of the H1 histone, we will also learn more about the repair of DNA damages on a molecular level. In order to provide the most efficient treatment, we need to know how the cells prevent and repair these damages.”

The team hope that their discovery will lead to greater levels of scientific interest in the H1 histone around the world, which could help researchers to understand the basis of diseases that are caused by changes in the genetic makeup of cells.

Posted by Jeanette Royston


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