Tsuneko Okazaki Tsuneko_Okazaki
Period One: Profile Period Two:Research Activity Period Three: Impact on Our Lives
Period Four: Virtual Science LabOkazaki Top Page
 Period Two: Research Activity
What sort of research did you do?
The cells of each human being contain in their nuclei two complete sets of genetic information, or genomes. When a new life is conceived, one genome from the mother and one from the father combine in the tiny fertilized egg. Since all cells of an organism carry the same genetic information, and an adult human being consists of approximately 60 trillion cells, the genetic material contained in the fertilized egg has to be copied exactly during each of about 60 trillion cell divisions. My research focused on the mechanism by which this genetic information is accurately replicated.

The genetic information within the cell nuclei is contained in molecules of deoxyribonucleic acid, or DNA. The genetic information contained in each cell's nucleus includes not only the codes for producing all the proteins in the human body but also information necessary to ensure that all the genetic data is passed to the next generation. DNA contains four bases known as A (adenine), T (thymine), G (guanine), and C (cytosine), which, lined up in various combinations of three along the DNA chain, create the codes for the 20 different amino acids that link up to form the proteins of the human body. Any change in that arrangement would result in the production of different proteins with different characteristics and functions.

Instead of being translated into a protein, some of the information encoded in the sequences of the DNA molecule controls the amount of protein created. Other sequences allow the DNA to replicate during cell division or ensure that the replicated DNA is correctly transmitted to the new cells. The ability to maintain all this genetic information without any alteration is extremely important if organisms are to reproduce.
What results has your research yielded?
The structure of the DNA molecule, first described in 1953, resembles a ladder with the two opposing side rails--called strands--linked together by the chemical pairing of the four bases: A with T, and G with C. Over the years, I have studied the process by which this "double helix" replicates.

The enzyme that synthesizes a new DNA strand from the parent strand--DNA polymerase--was discovered in 1956. However, early experiments on DNA replication had determined that this enzyme only allowed a new strand to grow in one direction, chemically speaking, along the original strand. And since the two DNA strands are oriented in opposite chemical directions, it was still unclear how copies of both strands could be created simultaneously. My husband Reiji Okazaki and I were among a large number of researchers attempting to unravel this mystery.

In the course of our research, Reiji and I discovered small fragments of DNA that appeared in the earliest stage of the replication process, and we hypothesized that these were somehow involved in synthesis of the problem strand. Working from this hypothesis, we found that the replication process occurs as follows: As the two strands of the original DNA molecule "unzip," synthesis along one of the strands occurs smoothly in the same direction as the "replication fork" (the spot where the parental forks into two separate strands). But along the other strand, which is oriented in the opposite direction, the process takes place discontinuously, by the successive synthesis of small fragments. As required by the properties of DNA polymerase, each of these fragments grows away from the replication fork. However, the successive emergence of these fragments proceeds in the direction of the fork, paralleling synthesis along the other strand. This was hailed as a major finding, and the fragments were named "Okazaki fragments."

After this important discovery, we decided to try to isolate the molecule (primer) that triggers the formation of the Okazaki fragments. The work was extremely difficult, and in the midst of it, I experience the greatest trial of my life as my husband and partner of many years fell critically ill and passed away. However, in 1978, I finally succeeded in isolating and analyzing the structure of this substance.
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