GENES may be able to send electrical signals to one another through a DNA information "superhighway", 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.
"It's a way of transmitting chemical information over a long distance that's dependent on a DNA sequence," 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).
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 "switches" 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. "We are talking about biologically relevant distances, and you can have strange fantasies about what the implications might be," says Barton.
But the team also found that specific sequences of DNA bases will stop the signals. These "insulating" regions consist of single or multiple pairings between the two DNA bases adenine (A) and thymine (T). "They serve as electronic hinges in the circuit," 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's 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 "electron traps" 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's interpretation is "highly speculative". "But this is better evidence than has been available before that you get electron transport along a DNA strand," he adds.
Lindahl rates as more important
Barton's 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.