DNA, the building block of the human genome, has the ability to change shape in unusual ways, according to an article published last week by University researchers in Nature.
Researchers used nuclear magnetic resonance technology, which is similar to a small-scale MRI imaging machine, to observe movements in individual bases in strands of DNA. It was then that University researcher Hashim Al-Hashimi, a University professor of chemistry and biophysics, and his team discovered something strange going on.
A molecule of DNA is typically layered according to the position of its nucleotides adenine, cytosine, guanine and thymine, which are abbreviated as A, C, G and T, respectively. The DNA double helix resembles the shape of a spiral staircase, but according to the research of Al-Hashimi and his colleagues, the various steps of this staircase are not rigid.
Al-Hashimi, who is the University’s Robert L. Kuczkowski Professor of Chemistry, worked with Rackham graduate student Evgenia Nikoliva, LSA senior Abigail Wise, Patrick O’Brien, an assistant professor of biological chemistry at the University, and colleagues from the University of California-Irvine, to determine these findings.
“Using the NMR technology was like having the first telescope, but rather than looking at the universe, we were looking at movements in small molecules,” Al-Hashimi said. “We observed clearly that the G and A (nucleotides) in the base pairs were doing something funny, moving in a way that was quite dramatic.”
These movements turned out to be 180 degree rotations, Al-Hashimi said.
The new positioning of the nucleotides classifies them as Hoogsteen base pairs, which have only previously been observed in damaged DNA or DNA proteins bound to molecules or drugs, Al-Hashimi said. Typical base pairs are called Watson-Crick base pairs, named after the scientists James Watson and Francis Crick, who discovered DNA in the 1950s.
According to Hashimi, the revelations could bring up new ideas about how DNA can store different types of genetic information.
For Nikolova, the findings were startling.
“We had no pre-conceived notion that we would discover something like this,” she said. “We were looking for interesting aspects of sequences … and we kind of came upon this.”
Though slight “gyration” of the DNA molecules in their respective positions can occur, the bases have generally been thought to remain stable, according to a University press release about Al-Hashimi and Nikolova’s findings.
By showing that bases can rotate, Al-Hashimi and his colleagues have opened the door to further study on the alternative pairings of DNA.
Structural changes that may occur around the Hoogsteen base pairs warrants further exploration, Nikolova said.
“The formation of one (Hoogsteen base pair) can facilitate the formation of another chain nearby,” she said.
Al-Hashimi also said if DNA is put under enough stress, the alternative form could become the standard form in the base pairs.
“I think that generally, now whenever we look at a structure, we’ll have to be wondering if there’s an alternative,” he said.