Duplication Process Suggests Alternative Approach to Cancer

Scientists at Dundee studying the processes behind cell duplication have made a discovery that they hope may help to tackle cancer one day. Professor Karim Labib and colleagues in the School of Life Sciences at Dundee had previously studied how proteins in simple yeast cells combine to build the replisome, a molecular ‘machine’ which plays a vital role in copying the double helix of DNA that is at the heart of each chromosome. The replisome is only built once during the life of each cell; it is then disassembled to ensure that cells just make one single copy of each chromosome.

They have found the process to be more complicated in animals, which have at least two different disassembly mechanisms and importantly, that the gene needed for one of these processes is lost in a number of human cancers.

“Ever since Watson and Crick first described the structure of DNA we have known that cells copy chromosomes, but we are still learning how it works,” said Professor Labib. “By looking at yeast, which is very similar genetically to humans, we discovered that one of the many components of the replisome undergoes a change called ‘ubiquitylation’, after the chromosomes have been copied, which marks the replisome for disassembly by the cell’s recycling machinery. This is a good thing, as genetic studies show that if the replisome is not taken apart but instead remains glued to the chromosomes, then this can lead to major problems.

“What we have now discovered is that the machinery that marks the yeast replisome for destruction doesn’t exist in animals, so there had to be something else driving this process. By studying a small worm called Caenorhabditis elegans we found that animals actually have two different mechanisms for replisome dissassembly. If one pathway fails to do its job then the second kicks in as a back-up.

“What makes this particularly interesting is that a gene required for the second mechanism is known to be mutated in a variety of human cancers, including some lymphomas, glioblastomas and myelomas. Our work with this gene in worms suggests a new way to treat the corresponding cancers in humans,” Professor Labib added.

The paper is published in the latest edition of the journal Nature Cell Biology.