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Monday, 8 October, 2001, 11:45 GMT 12:45 UK
What did Nobel winners do?
dna
The findings help doctors developing cancer treatments
The trio who have been awarded the Nobel Prize for Medicine made some of the most important recent advances in molecular biology.

BBC News Online examines the discoveries of each, and assesses their future importance.

The billions of cells in the human body are continuously dividing to replace those which grow old and die.

Gaining understanding of the cycle of division of a normal healthy cells is one of the most significant breakthroughs in recent years.

This may help scientists understand what is going wrong in cells where multiplication is uncontrolled - such as cancer cells.

Professor Lee Hartwell

Professor Hartwell's work in this area began in the 1960s, when he chose to study the cell cycle of humble baker's yeast cells.

By genetically modifying the cells, he managed to find more than 100 genes which seemed to play some sort of role in the cycle - calling them cell division cycle genes.

One of these genes, called CDC28, seemed to control the important first step in the cycle - Hartwell called it the "start" gene.

His work also included the irradiation of cells to test how cells reacted when their genetic material was damaged by radiation.

He found that the normal process of cell division was halted temporarily to allow time for the damaged DNA to be repaired.

This he dubbed a "checkpoint", and went on to discover similar checkpoints which made sure that cells were passing through the cell division process in the correct manner.

More recently, his work has produced the revelation that cancer cells somehow manage to evade these "checkpoints" as they continue to divide uncontrollably.

His studies form the foundation for hundreds of scientists who are trying to break the "vicious cell cycle" which allows cancer cells to proliferate.

Sir Paul Nurse

Sir Paul started by using a different kind of yeast as his model, finding a gene in this which again played an important part in controlling more than one element of the cell division cycle.

Then he moved his work into human cells - and Sir Paul found the gene in humans which corresponded to "start" in the yeasts.

The discovery, 1987, that humans shared this mechanism was pivotal.

This gene, called CDK1 (cyclin dependent kinase 1), appeared to have a role at more than one point in the cell cycle.

The proteins for which the various CDK genes encode have been likened to the "engine" of the cell cycle - providing the impetus to drive the cell from one stage into the next.

Dr Tim Hunt

Although, by the early 1980s, the "Start" genes had been discovered in yeasts, little was known the process of regulating cell division worked.

Dr Hunt was the first to discover protein molecules called cyclins, which appeared to be significant in regulating the way in which CDK worked during the cycle.

If CDK is the engine, then cyclins are the "gearbox".

They bind to CDK molecules, and regulate their activity.

The levels of cyclins vary during different points in the cell cycle.

Dr Hunt also found cyclins in other species, and approximately 10 have been identified in human cells.

Why are their discoveries significant?

It is thought that defective cell cycle control may cause genetic material to be inadequately passed from the parent cell to the two new daughter cells.

These alterations to the chromosomes, in which parts are lost or rearranged, is likely to be important in the development of cancer cells.

It is possible that too much CDK in a cells may disrupt the cell cycle, and potentially cause these problems.

Increased levels of CDK molecules and cyclins have been found in some human tumours, such as breast cancer.

In this case, treatments which inhibit the working of CDK molecules may have some promise as anti-cancer therapies.

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