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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. |
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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. |