DNA Polymerase

Bruce Michael Alberts was born in Chicago, Illinois in 1938. His interest in science began in seventh grade when he had to explore the inside of a television set and explain how it worked. This interest was further stoked during his junior year in high school when he had the chance to play with reagents and set off explosions in science class. He recalls, “we could see chemistry as being real. That was quite different from just reading about chemistry” (1). Alberts enjoyed the hands-on aspects of science so much that he decided to pursue a career that involved chemistry. During his high school's Career Night, he attended lectures by the two speakers who used chemistry in their jobs: a chemical engineer and a physician. The engineer drew dull pictures of pipes and tanks on the blackboard, whereas the physician spoke about the importance of science for medicine. At that point, Alberts decided to become a physician.

However, Alberts' hopes for explosions and hands-on experiments were dashed when he arrived at Harvard University in 1956 and realized the course work consisted mostly of memorizing facts and performing simple experiments in laboratory sections. Fortunately, he was invited to work in Paul Doty's laboratory where he discovered that the college science he had been exposed to was not at all like actual science. Working on deciphering how errors in DNA and RNA base pairing affected their helical structure, Alberts was able to publish his results in the Proceedings of the National Academy of Sciences and Nature (2, 3). Suddenly, medical school did not seem as appealing as pure science, and Alberts decided to pursue a doctorate in biophysics at Harvard after graduating in 1960 with an A.B. in Biochemical Sciences.

Working in Doty's laboratory on DNA replication, Alberts earned his doctorate in 1965. He then spent the following year as a postdoctoral fellow at the University of Geneva with Alfred Tissières and Richard Epstein studying the phage T4 genes involved in DNA replication. In 1966, Alberts joined the Department of Biochemical Sciences at Princeton University as an Assistant Professor. He eventually became Damon Pfeiffer Professor of Life Sciences in 1973 and was the Acting Chairman of the Department of Biochemical Sciences from 1973 to 1974 and the Associate Chairman from 1974 to 1975. In 1976, Alberts left Princeton to become Professor and Vice Chair of the Department of Biochemistry and Biophysics at the University of California, San Francisco. In 1980, he was awarded an American Cancer Society Lifetime Research Professorship, and in 1985, he was named Chairman of the UCSF Department of Biochemistry and Biophysics.

Greatly influenced by his graduate and postdoctoral studies, Alberts' research has continued to focus on DNA replication. He is noted particularly for his extensive study of the protein complexes that allow chromosomes to be replicated. For example, while at Princeton, Alberts discovered the T4 gene 32 protein. This proved to be the first example of a single-strand DNA-binding protein, a structural protein that plays an important role in DNA processes in all organisms (4). The two Journal of Biological Chemistry (JBC) Classics reprinted here deal with Alberts' explanation of how DNA polymerase can replicate both the leading and lagging DNA strands simultaneously.