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DNA size a crucial factor in genetic mutations, study finds

Researchers at Stanford University have created a larger-than-normal DNA molecule that is copied almost as efficiently as natural DNA. The findings, reported in the Oct. 25 online edition of the Proceedings of the National Academy of Sciences (PNAS), may reveal new insights into how genetic mutations-tiny mistakes that occur during DNA replication-arise. The discovery was made in the laboratory of Eric Kool, a professor of chemistry at Stanford and co-author of the PNAS study.

DNA, the genetic encoder of life, comes in two parallel strands that form a double helix. It's like a long, twisted ladder where each rung consists of two molecules that form a base pair. DNA has four bases: adenosine (A), thymine (T), guanine (G) and cytosine (C). A always pairs with T, and G with C. To copy itself, the DNA molecule unwinds and splits. Either strand is now a template to build a new DNA molecule. An enzyme-a protein that speeds the reaction, in this case the bacteria E. coli's DNA polymerase I-moves along the template and selects the corresponding base to create a new base pair.

DNA bases fit into a specialized site on the enzyme before they are bonded to the template. Kool wanted to see how the enzyme reacts if the bases are not the usual size. ''The idea was to see how DNA replication depends on size,'' Kool says.

The researchers investigated it by offering bases of different sizes to the DNA polymerase I enzyme and measuring how accurately the enzyme made new DNA copies. About once every 10,000 to 100,000 times the enzyme will put in the wrong base, choosing for instance a G instead of a T to pair with an A. The rate that the enzyme accurately copies DNA is known as its efficiency.

These rare and random mistakes can cause genetic mutations. While we tend to heap negative connotations onto the term, some mutations create new traits that actually benefit the organism or yield no effect. These small-scale changes, collectively called genetic dri
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Contact: Mark Shwartz
mshwartz@stanford.edu
650-723-9296
Stanford University
26-Oct-2005


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