Scientists at the Medical Research Council Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU) at the University of Dundee have solved an important part of the mystery about one of the most fundamental processes in cell biology.
The process by which cells copy their own chromosomes and then make new cells is vital to all of life. The chromosomes contain the genetic blueprint that makes us what we are and this information must be copied perfectly for new cells to survive and carry out their function.
When the copying process goes wrong, it can lead to cancer as abnormal cells are created.
In a research paper published in the journal Science, Professor Karim Labib and Marija Maric in the MRC-PPU at the College of Life Sciences at Dundee have described for the first time a key part of this process.
“The process by which cells copy chromosomes has fascinated biologists ever since Watson and Crick first described the structure of DNA, but we are still quite a way from having a complete picture of how it works,” said Professor Labib.
“Our work describes a process that takes place when cells finish copying their chromosomes, which is vital for the genetic ‘blueprint’ to be passed on from one generation to the next. We already knew that eleven proteins in the cell combine to build a molecular ‘machine’ called the DNA helicase, which plays a vital role in copying the double helix of DNA that is at the heart of each chromosome.
“This machine unwinds the two strands of the DNA double helix, so that each strand can then be copied. It is vital that the helicase is only built once during the life of each cell, and then is taken apart or disassembled once it has done its job, so that cells just make one single copy of each chromosome. Until now we didn’t know how the disassembly process worked.
“We have discovered that one of the 11 components of the helicase undergoes a change, in a process called ubiquitylation, which makes it fall out of the `machine’ once all of the chromosome has been copied. Taking out one component of the helicase means that the other proteins cannot continue to stick together and the `machine’ falls apart.
“It turns out that this is a very good thing, as genetic studies show that if the helicase does not come apart but instead remains glued to the chromosomes, then this leads to major problems.”
Professor Labib said that the work was another significant step towards understanding the processes at the heart of our cells, which are important as we try to develop new treatments to tackle human diseases like cancer.
“This is one of the fundamental areas of biology that goes wrong in cancer – almost any time that we see cancer developing, one of the things that has gone wrong early in the process is that the chromosome copying machinery has not worked properly,” said Professor Labib.
“One of the goals in cancer research is to understand the normal biology that goes wrong in cancer cells, because only then can we look for better ways to kill cancer cells without hurting the rest of our body. This area of chromosome replication has been of major interest for the last couple of decades, as we uncover more and more about how it works.
“The work done by my team here in Dundee, funded by the Medical Research Council, Cancer Research UK and the Wellcome Trust, has given us another important part of the picture.”