Structural Biochemistry/James C. Wang

James C. Wang is a biochemist who had taught at Harvard University and University of California, Berkeley. He is the person who discovered DNA topoisomerase, which was a new enzyme at that time that was able to convert a DNA ring from one form to another. After its discovery, researchers and scientists were able to study how DNA strands and double helixes were passed from one another.

Early Life

Wang was born in the Jiangsu Province of China during a time of war and tension between China and Japan. Although his time in school was constantly being interrupted, he received a decent education from his mother and through self-learning. Majoring (graduating) in chemical engineering at the National Taiwan University, he continued to pursue his love for chemistry working as a lecturer after graduation. He continued his education and received his PhD in Physical Chemistry at the University of Missouri. Soon after, he received a position to work with DNA alongside with Norman Davidson at the California Institute of Technology in 1964.

Discovery

While Wang was working with DNA, he started to question why isolated DNA rings were negatively supercoiled. Back then, scientists answered this questions with two different models - one, because the helical structure of DNA inside and outside a cell were different; or two, because of the unique structure within an intracellular DNA where the two complementary strands were kept apart. In other words, the first model suggested that an increase in the number of negative supercoils correlated with its size, while the second suggested that the number of negative supercoils would be independent to its size. Wang decided to look into these two models under identical conditions and discovered that a 25-fold range would have a 1.5 factor of negative coils per length.

In an accidental discovery, Wang left centrifuge tubes containing lysate with infected E. coli cells unattended only to come back with relaxed DNA rings 2.5 hours later. From that small incident, Wang later discovered that supercoiled removal activity and DNA ligase did not correlate with each other. Instead, the "w" protein was the one that removed negative supercoils.

The 1970s was a time of breakthrough regarding DNA research. James Champoux and Renato Dulbecco discovered an activity in mouse cell that relaxed both negative and positive supercoiled DNA with the presence of Magnesium in 1972, and in 1976, Martin Gellert discovered an E. coli enzyme that catalyzed ATP-dependent DNA (DNA gyrase). In 1979, Wang named these enzymes "topoisomerase" because of their ability to interconvert topological isomers. From there, he was also able to prove that positively supercoiled DNA can be relaxed if a short single-stranded loop is inserted into the DNA.

References

http://www.annualreviews.org/doi/pdf/10.1146/annurev.biochem.78.030107.090101