UC Scientists Study Cancer's Ferocious Proliferation

Cancer cells are the adolescent delinquents of the human body, growing at an astounding rate and wrecking havoc by refusing to obey normal cell regulations.

UC Berkeley scientists have uncovered another aspect of the cancer cell's nonconformist stance-where they keep the enzymes, or molecular machines, that regulate their biological clocks.

While a normal human cell can only divide a limited number of times, most cancerous cells are capable of dividing indefinitely, becoming effectively immortal.

Cancer's fountain of youth is an enzyme known as telomerase, which is not manufactured in most normal cells.

As children at the beach might labor to keep their sand creations from being destroyed by pounding waves, telomerase works by lengthening chromosomes at their ends, replenishing the tiny bits of DNA that are lost with each successive duplication.

Without telomerase, the rising tide inevitably consumes the buffer DNA, and the cell must cease reproduction.

"Short telomeres will prevent cells from replicating," said UC Berkeley research fellow Judy Wong.

Wong, along with molecular and cell biology professor Kathleen Collins, induced some non-cancerous cells to produce telomerase.

The molecules were then tagged with a green fluorescent protein to track their movement within the cell.

The scientists observed that, in these healthy cells, telomerase was usually kept sequestered from the DNA sequences upon which it acts.

Only during a short part of the cell cycle, when DNA is being replicated, is telomerase unleashed to perform its restorative job.

"It shows for the first time that telomerase is regulated not only by whether it's present, but where it is in the cell," said UC San Francisco biochemistry and biophysics professor Elizabeth Blackburn.

Blackburn, who discovered telomerase in the 1980s while at UC Berkeley, compared the recent research to observing yellow school buses from outer space.

In the daytime, when the buses are busy taking children around, it would be difficult to detect them. At night, when sitting together in a bus depot, they are much easier to see.

From these observations, one may falsely conclude that buses function primarily inside the bus depot at night, when they are concentrated together.

Likewise, telomerase functions only when it is released and allowed to intermingle with DNA strands.

In cancerous cells, telomerase is almost always at work extending chromosome ends.

In cancerous cells, it is speculated that telomerase may also function in the repair of broken strands of DNA, Wong said.

Since telomerase adds a DNA sequence normally found at chromosome ends, arbitrarily appending it to the middle of the chromosome destabalizes a normal cell.

To test this hypothesis, the researchers subjected cells to radiation, breaking down their DNA.

The scientists found that in both normal and cancerous cells, telomerase was shuttled away from the DNA.

"The relocation of telomerase during the cell cycle, in transformed cells (which are en route to being cancerous), and following exposure to ionizing radiation is an exciting discovery that further illustrates the importance of telomerase in maintaining chromosome stability," said UCSF biophysics professor John Murnane.

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