5 April 1999. Fred Van Leeuwen and his colleagues reported last
year that some neurons in Alzheimer's patients contain mutant
RNA coding for APP and ubiquitin, despite the fact that the DNA
from which the RNA had been transcribed was not mutated. By what
process could "clean" DNA produce "dirty" RNA? One candidate is
a phenomenon called transcriptional bypass, wherein damage to
the template DNA goes uncorrected and becomes responsible for
coding an erroneous base into the RNA. This can happen if, for
example, the DNA base cytosine is deaminated, producing the
aberrant base uracil. Rather than correcting this error, the
transcriptional machinery treats uracil as the proper, and
structurally similar, base thymine. Adenine, rather than the
appropriate base, guanine, is then transcribed into the RNA,
introducing an error that is propagated into protein production.
Transcriptional bypass has been demonstrated in vitro, where it
can efficiently generate mutant proteins, but Viwanathan and
colleagues have just publi