Supercomputers have helped scientists find a surprising link between cross-shaped (or cruciform) pieces of DNA and human cancer, according to a study carried out at The University of Texas at Austin (UT Austin). DNA naturally folds itself into cross-shaped structures called cruciforms that jut out along the sprawling length of its double helix. DNA cruciforms are abundant; scientists estimate as many as 500,000 cruciform-forming sequences may exist on average in a normal human genome. Over 80 percent of DNA cruciforms are considered small, i.e., fewer than 100 base pairs of DNA. Small cruciforms enable DNA replication and gene expression, essential for human life. But scientists have also suspected these small cruciforms -- a structure of DNA itself -- to be linked to mutations that can elevate cancer risk. DNA cruciforms are created by short inverted repeats of the nucleotides adenine, thymine, cytosine, and guanine that form the bases of DNA structure. Inverted repeats are DNA nucleotide sequences followed by their reverse complement. They're like a palindrome, a word phrase that reads the same backwards and forwards, such as “Never a foot too far even.” The UT Austin study found that small DNA cruciforms are mutagenic, altering DNA in a way that can increase risk of cancer in yeast, monkeys, and in humans. High-performance computing at UT Austin's Texas Advanced Computing Center (TACC) with the Stampede and Lonestar supercomputers helped the researchers find short, inverted repeats of 30 base pairs and under in a reference database of mutations in human cancer that are somatic, meaning not inherited. DNA strands commonly break in human cells. Repair proteins fuse the broken end of one DNA strand to the broken end of another.
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