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Common genetic damages in non-dividing cells lead to the creation of mutant proteins

ATLANTA--Two types of DNA damage that frequently befall most cells on an everyday basis can lead to the creation of damaged proteins that may contribute to neurodegeneration, aging and cancer, according to research by scientists at Emory University School of Medicine, published in the October 23 issue of the journal Molecular Cell.

The investigators used e. coli cells as a model system to study specific kinds of genetic damages that occur in all non-dividing cells undergoing transcription the everyday activity in which cells produce the proteins necessary to carry out bodily processes. The vast majority of scientists studying genetic mutations have focused instead on the cell replication process, in which damaged and unrepaired DNA within multiplying cells can be copied before cells divide and passed along to a new generation of cells. Most of the cells within organisms are no longer replicating, however, and instead spend their time manufacturing proteins.

Paul W. Doetsch, PhD, professor of biochemistry at Emory University School of Medicine, lead author Damien Bregeon, PhD, an Emory postdoctoral fellow, and their colleagues discovered that in e.coli cells, two of the most frequently occurring spontaneous DNA damages that cells in all organisms are exposed to on a daily basis cause transcriptional mutagenesis (TM). TM occurs when cells with damaged DNA produce bad messages during transcription that lead to the creation of mutant proteins.

During transcription, cells make an RNA copy of the combinations of base sequences that make up the genes on the DNA molecule. This RNA copy serves as a blueprint for manufacturing particular proteins. One type of spontaneous genetic damage occurs in non-dividing cells when cytosine (C), one of the four amino-acid bases (A, T, G, and C) spontaneously changes to uracil (U). This common substitution causes genetic miscoding that can lead to TM and the manufacture of mutant proteins during transcripti
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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University Health Sciences Center
22-Oct-2003


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