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Scientists step closer to understanding cancer biology

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The search for new cancer treatments has taken a significant step forward with a new insight into how cells multiply, scientists have announced.

Dundee University researchers have identified the process by which DNA unwinds, duplicates and ensures that only a single copy of each chromosome is made.

A failure in this process is one of the fundamental areas of biology that goes wrong in cancer, scientists said.

“Until now we didn’t know how the disassembly process worked”

Karim Labib

The work, funded by the Medical Research Council, Cancer Research UK and the Wellcome Trust, could lead to better methods to safely kill cancer cells, they added.

In a research paper published in the journal Science, Professor Karim Labib and Marija Maric from the College of Life Sciences at Dundee have described for the first time a key part of the multiplication process.

Professor Labib said: “We already knew that 11 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,” he said.


DNA helicase plays a vital role in copying the double helix

“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,” he added.

“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,” said Professor Labib.

“Taking out one component of the helicase means that the other proteins cannot continue to stick together and the ‘machine’ falls apart,” he said.

“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.”

University of Dundee

Karim Labib

He added: “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.

“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.”



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