Staff Editor
Mice have some funky DNA where, at least over stretches, they add a third strand in. According to a recently published paper called “Triple-helix potential of the mouse genome,” a team of researchers demonstrate that we don’t really understand how mice are genetically programmed. Maybe they really ARE the pan-dimensional beings who commissioned the Earth.
Three strands of DNA
H-DNA, Kaku Maekawa and his team write, “is a non–B-form DNA structure containing intramolecular triplex and single-stranded DNA (ssDNA) regions.”
That has impacts on genome stability and “processes such as replication and transcription,” but the team admits, the non-B DNA-forming potentials of mice “are not fully understood.”
What they do know is that “the triplex-forming potential of H-DNA motifs in the mouse genome can be evaluated by a deep-sequencing technology.” Only another scientist cares about the gory details. The gist of it is that certain sequences of DNA can occasionally “fold” into “a triple-helix–containing non–B-form DNA structure called H-DNA.” Mice aren’t the only critters who can do it.
“H-DNA–forming sequences occur frequently in many eukaryotic genomes, including in mammals, and multiple lines of evidence indicate that these motifs are mutagenic and can impinge on DNA replication, transcription, and other aspects of genome function.”
Their paper goes through all the ins and outs of “triplex-forming potential of H-DNA motifs in the mouse genome” which they evaluate “using S1-sequencing” to start with single-stranded DNA and generate “deep-sequencing libraries that report on the position of ssDNA throughout the genome.”
Trust us, it works, they assure.
Hoogsteen triplets
Fasten your seat belts, the ride’s going to get bumpy here. One of the structures they focused on, “consists of an intramolecular triplex plus single-stranded DNA.”
The “duplex from one half of the H-DNA motif forms Hoogsteen triplets with a ‘third strand‘ contributed by melting the duplex in the other half of the motif.” They note the result usually turns out to be “Polypyrimidine•polypurine mirror repeats.”
They end up with a structure containing common features. “H-DNA contains three ssDNA regions that we will refer to as the central loop, orphan strand, and junction.”
The central loop part forms a “ssDNA hairpin between the triplex-forming segments on the same strand.” That’s where the third side of the ladder comes from.
The DNA “junction” is “is a short ssDNA region between the triplex and the flanking duplex.” Finally, the “orphan strand is complementary to the central loop, the third strand, and the junction.”
They want everyone to know that the experiments conformed to the Office of Laboratory Animal Welfare regulations and “were approved by the Memorial Sloan Kettering Cancer Center Institutional Animal Care and Use Committee.“
