In this podcast, Karen Vasquez and Albino Bacolla of the University of Texas at Austin describe how TACC supercomputers have helped scientists find a surprising link between cross-shaped pieces of DNA and human cancer.
DNA naturally folds itself into cross-shaped structures called cruciforms that enable DNA replication. In their study, they’ve found is that these tiny cruciforms – just a small shape of normal DNA – are linked to mutations that can elevate cancer risk. High performance computing on 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.
We have also studied the potential mechanisms that are involved in the interplays among alternative DNA structures and cancer development, said Vasquez. “Our team has discovered at least two different mechanistic pathways: one involving DNA replication, where these unusual structures cause a roadblock to DNA replication; the other pathway is independent of that, where DNA repair proteins, we think, recognize these alternative DNA structures as damage, even though there is no damage per se. The cells try to process the structures as damage, but they are really processing naturally occurring unusual DNA formations and not actual damage. An abortive error prone repair process can then cause DNA double-strand breaks and lead to serious problems including neoplastic transformation.”
According to Bacolla, the study involved two billion iteration in total: 20,000 translocations from human cancers from the COSMIC database; 200 bases of DNA for each translocation; and about 200-400 iterations at each position.
It would not have been possible to do this job without the TACC resources, said Bacolla. “It’s a wonderful opportunity for researchers at UT Austin.”