Spontaneous chemical changes occurring within the DNA of non-dividing cells may result in the development of mutant proteins with potentially serious consequences for the development of degenerative neurological diseases or cancer. Findings by Emory University scientist Paul Doetsch, Ph.D., reported in the April 2, 1999 issue of Science, provide a new explanation for why and how terminally differentiated cells -- those that are no longer dividing and replicating -- express unrepaired genetic damage. Co-authors of the study were graduate student Anand Viswanathan and Ho Jin You, M.D., Ph.D.
Most of the cells within the adult human body are no longer replicating, but are responsible for manufacturing the proteins necessary to carry out everyday bodily processes. Yet most research on cellular DNA damage and repair mechanisms has focused on the cell replication process, where damaged and unrepaired DNA can result in errors when DNA is copied before cells divide.
Dr. Doetsch and his colleagues concentrated on non-dividing cells, which go through a process called transcription in order to manufacture proteins. During transcription, the cell first makes an RNA copy of the DNA molecule by using an RNA polymerase -- a specialized protein that reads the DNA genetic code imprinted on one of the two DNA strands. The polymerase then turns the genetic code into an RNA genetic code. The base sequence code on the RNA, in turn, serves as a blueprint that "codes" for a particular protein.
The Emory investigators studied a particular type of spontaneous damage
occurring in cytosine, one of the four amino-acid bases (A, T, G, and C) that
are combined in different sequences within the DNA to make genes. In a common
chemical change, cytosine may lose one of its components and change to uracil, a
base that is normally found only in RNA. Since uracil (U) acts more like the T
base than it does the C base, it causes genetic miscoding that can lead to
Contact: Holly Korschun
Emory University Health Sciences Center