Magazine article Science News

Not So Silent: Mutation Alters Protein but Not Its Components

Magazine article Science News

Not So Silent: Mutation Alters Protein but Not Its Components

Article excerpt

A single swap in the letters of a gene's sequence could modify the protein it encodes, even if the switch doesn't change which amino acids make up the molecule, researchers report. The finding could upset a central view in biology--that proteins made of the same amino acids are identical.

DNA contains components called nucleotides, symbolized by the letters A, T, G, and C. Each block of three of these letters--known as a codon--signals a cell's protein-making machinery to add a particular amino acid to a lengthening chain. Most of the 20 amino acids are each encoded by two or more of these three-letter combinations.

Biologists have long held that swapping one codon for another doesn't change the resulting protein's structure, as long as both codons instruct the machinery to insert the same amino acid. However, experiments by Michael Gottesman of the National Cancer Institute in Bethesda, Md., and his colleagues led the team to suspect that those silent mutations might lead to significant differences.

Gottesman's team investigates why some cancers don't respond to chemotherapy. They've found that a tiny pump, called P-glycoprotein, located on tumor cells' surfaces, can pull drugs out of cells. Some drugs are ineffective against cancer cells that have certain forms of P-glycoprotein. The researchers had noticed that individual cancer patients' pumps sometimes show differences in function, even when the pumps' proteins are made of identical combinations of amino acids. …

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