GENES may be able to send electrical signals to one another through a DNA
information 鈥渟uperhighway鈥�, according to Jacqueline Barton and her colleagues at
the California Institute of Technology in Pasadena. The team showed that single
electrons can shoot far enough along DNA to influence gene activity.
鈥淚t鈥檚 a way of transmitting chemical information over a long distance that鈥檚
dependent on a DNA sequence,鈥� says Barton, whose results appear in Chemistry
& Biology (vol 6, number 2, p 85). She speculates that the electrical
signals might help to switch genes that are far apart on and off.
Last year Barton and her colleagues showed that electrons can pass through
short stretches of DNA by hopping between the overlapping electron clouds of
adjacent nucleotide bases, the molecular building blocks of DNA
(This Week, 22 August 1998, p 21).
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Together, the disc-shaped electron clouds of each individual base form stacks
which serve as an electron-rich pathway for conducting electrical signals.
What surprised the chemists this time, however, was the sheer distance over
which a signal could travel. They found that signals could span 60-base chunks
of DNA 20 nanometres long, a stretch long enough to code for 20 amino acids. DNA
promoters, the molecular 鈥渟witches鈥� that turn on adjacent genes, are typically
this length. The team concluded that in theory, there is no limit to the
distance signals could travel along DNA. 鈥淲e are talking about biologically
relevant distances, and you can have strange fantasies about what the
implications might be,鈥� says Barton.
But the team also found that specific sequences of DNA bases will stop the
signals. These 鈥渋nsulating鈥� regions consist of single or multiple pairings
between the two DNA bases adenine (A) and thymine (T). 鈥淭hey serve as electronic
hinges in the circuit,鈥� Barton says.
The investigators speculate that nature may have engineered these insulators
to protect vital genes from electrical damage. In fact, they initially set out
to study this type of damage to DNA, which can be caused either by harmful
chemical agents called free radicals, or by radiation.
They inflicted this kind of damage on synthetic DNA with ruthenium-based ions
which mimic the effects of natural free radicals, which may cause cancer.
Like all oxidising agents, the ruthenium ions lack an electron. In the
experiments, they steal one from guanine, the nucleotide base with the weakest
hold on its outermost electron. Barton鈥檚 team found this happened even if the
guanine base was as much as 60 bases away from the ion. But the presence of A
and T pairings blocked this electron transfer. Baton speculates these 鈥渆lectron
traps鈥� might prevent the sort of DNA damage that leads to cancer.
However, Tom Lindahl, a specialist in the study of DNA damage at the Imperial
Cancer Research Fund in South Mimms, Hertfordshire, says Barton鈥檚 interpretation
is 鈥渉ighly speculative鈥�. 鈥淏ut this is better evidence than has been available
before that you get electron transport along a DNA strand,鈥� he adds.
Lindahl rates as more important Barton鈥檚 finding that DNA can be damaged away
from the original oxidation site. This might help explain how single oxidising
agents might be able to trigger clusters of mutations that can potentially lead
to cancer, he says.