Scientists discover how key enzyme involved in aging, cancer assembles

A model representing the interaction of the p65 protein with telomerase RNA. The RNA backbone of telomerase (multicolored) is shown interacting with three different parts of the p65 protein (shown in gold, blue, and light green). Credit: Mahavir Singh, Juli Feigon/UCLA Chemistry and Biochemistry

(Phys.org) -- UCLA biochemists have mapped the structure of a key proteinRNA complex that is required for the assembly of telomerase, an enzyme important in both cancer and aging.

The researchers found that a region at the end of the p65 protein that includes a flexible tail is responsible for bending telomerase's RNA backbone in order to create a scaffold for the assembly of other protein building blocks. Understanding this protein, which is found in a type of single-celled organism that lives in fresh water ponds, may help researchers predict the function of similar proteins in humans and other organisms.

The study was published June 14 in the online edition of the journal Molecular Cell and is scheduled for publication in the print edition on July 13.

The genetic code of both the single-celled protozoan Tetrahymena and humans is stored within long strands of DNA packaged neatly within chromosomes. The telomerase enzyme helps create telomeres protective caps at the ends of the chromosomes that prevent the degradation of our DNA, said Juli Feigon, a UCLA professor of chemistry and biochemistry and senior author of the study.

Each time the cell divides, the telomeres shorten, acting like the slow-burning fuse of a time bomb. After many divisions, the telomeres become eroded to a point that can trigger cell death.

Cells with abnormally high levels of telomerase activity constantly rebuild their protective chromosomal caps, allowing them to replicate indefinitely and become, essentially, immortal. Yet undying cells generally prove to be more of a curse than a blessing, Feigon said.

"Telomerase is not very active in most of our cells because we don't want them to live forever," said Feigon, who is also a researcher at UCLA's Molecular Biology Institute and a member of the National Academy of Sciences. "After many generations, DNA damage builds up and we wouldn't want to pass those errors on to subsequent cells."

Overactive telomerase has potentially lethal consequences far beyond the propagation of erroneous DNA. The enzyme is particularly lively within cancer cells, which prevents them from dying out naturally. Finding a way to turn off telomerase in cancer cells might help prevent the diseased cells from multiplying.

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Scientists discover how key enzyme involved in aging, cancer assembles

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