Journalists from The Scientist (www.the-scientist.com/news-opinion/some-viruses-use-an-alternative-genetic-alphabet-68726) and Nature (www.nature.com/articles/d41586-021-01157-x) recently interviewed David Dunlap, PhD,. He was asked to comment on recent discoveries reported in three articles published in Scie
nce on April 29, 2021 of 60 organisms whose genome contains diaminopurine (DAP) instead of adenine and enzymes responsible for incorporating DAP into DNA.
For over forty years prior, only one cyanophage, a virus that infects a cyanobacterium, contained diaminopurine (DAP) in place of adenine. Diaminopurine establishes three hydrogen bonds with thymine instead of the usual two that form between adenine and thymine. A few years ago, David developed protocols to synthesize kbp-long DAP-substituted DNA using the polymerase chain reaction. Together with collaborators in the laboratory of Francesco Mantegazza in Milan Italy and the laboratory of Laura Finzi, he has published studies detailing the relative stiffness of DAP-DNA compared to that with adenine. With Monica Fernandez, a former postdoc in the physics department, and Qing Sho, a former graduate student, David found that the different mechanical properties of DAP- and adenine-containing DNA can affect enzymatic activities of DNA processing enzymes like topoisomerases (doi.org/10.1016/j.jmb.2015.04.006).
Currently, with Qing, the Finzi and Mantegazza laboratories, David is working to characterize the torsional characteristics of DAP-DNA and its phase transition to left-handed DNA. The altered mechanical characteristics of DNA with base substitutions is an active field of investigation at the intersection of biochemistry, physics, and biology with potential applications in biotechnology as well.