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Weizmann Institute scientists discover a molecular security mechanism for keeping mutations in check

Everyone knows mutations ?genetic mistakes in DNA, the material of heredity ?are bad: The more mutations in the cell's DNA, the higher the risk of cancer developing. But in the last few years it has become clear that the very processes that generate mutations, if they take place at a relatively low frequency, can actually protect us from cancer. How does the body know how to keep these processes in check, making sure they don't rocket out of control, causing a sharp rise in our cancer risk?

A preliminary answer to this question has come out of research carried out by Prof. Zvi Livneh and research student Sharon Avkin, along with research student Leanne Toube and Dr. Ziv Sevilya of the Biological Chemistry Department, and Prof. Moshe Oren of the Molecular Cell Biology Department, along with two American colleagues. The results of their study appeared recently in the scientific journal Molecular Cell.

The instruments of DNA copying (which takes place prior to cell division) are members of a family of enzymes called DNA polymerase. DNA polymerase travels along one strand of the double stranded molecule, reading each bit of genetic material and copying as it goes along, to create new DNA that will be passed on to the daughter cell at cell division. This enzyme can be a stickler for accuracy ?if it runs into damage from radiation or exposure to harmful substances on the DNA strand, it can stop in its tracks, unable to continue copying. A stoppage of this sort spells death for the cell. But not all damage to DNA is critical and, to avoid the wholesale death of cells, a second type of DNA polymerase, one that is more "careless" and can improvise when it hits a snag, evolved in the cell. "Error-prone DNA repair," as it's called, is based on a compromise: The cell lives, but at the price of allowing genetic mutations to be carried over in cell division.

The body's solution to minimizing mutations is to have no fewer than ten different "careless" enzy
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Source:American Committee for the Weizmann Institute of Science


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