DNA: A sloppier copier

Novel, Mutation-Prone DNA Replication Enzyme Identified

University researchers have resolved an enigma of more than three decades standing by definitively establishing how ultraviolet radiation causes genetic mutation in a common bacteria.

The resolution is a surprise. While radiation is the stimulus, the group found, most of the resulting mutations are self-inflicted wounds, caused by a highly error-prone emergency DNA copying system of a novel kind.

The discovery of this system, announced in a paper in the Aug. 3 issue of the Proceedings of the National Academy of Sciences, sheds light on a fundamental cell survival process. The process is highly significant in aging, cancer and species evolution. It may even offer a clue to the solution of another long-standing mystery -- why the immune system's globulin genes are so prone to error.

A research team led by Myron F. Goodman, Ph.D., of the University of Southern California, studied a complex of evanescent substances seen at sites of DNA replication in Escherichia coli bacteria exposed to ultraviolet light. The team has established that the complex is a DNA polymerase, the fifth DNA replicating enzyme to be identified in the organism.

The new enzyme, named "pol V," differs in two significant ways from pols I, II and III, which are well-known enzymes.

First, pol V is a highly inaccurate replicator of DNA. While the other three enzyme systems copy and reproduce information-carrying sequences of the chemical bases in the DNA alphabet with an error rate of fewer than one mistake per million bases, the newly discovered enzyme is about 100 times more error-prone.

Second, pol V's structure is quite distinct from the others', which are all variations on a single design first identified in 1956 by Arthur Kornberg in work for which he shared the 1959 Nobel Prize in medicine. Dr. Goodman, a professor of biological sciences in the USC College of Letters, Arts and Sciences, notes

Contact: mankin@usc.edu
University of Southern California

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