Do bzh a n s k y, T h e o d o s i us 577
Further Reading
Bates AD and Maxwell A (1993) DNA Topology, pp. 1±114.
Oxford: IRL Press.
Cozzarelli NR and Wang JC (eds) (1990) DNA Topology and its
Biological Effects, pp. 1±480. Plainview, NY: Cold Spring Har-
bor Laboratory Press.
Lilley DMJ, Chen D and Bowater RP (1996) DNA supercoiling
and transcription: topological coupling of promoters. Quar-
terly Review of Biophysics 29: 203±225.
Murchie AIH and Lilley DMJ (1992) Supercoiled DNA and cruci-
form structures. Methods in Enzymology 211: 158±180.
Sherratt DJ and Wigley DB (1998) Conserved themes but
novel activities in recombinases and topoisomerases. Cell
93: 149±152.
Reference
Liu LF and Wang JC (1987) Supercoiling of the DNA template
during transcription. Proceedings of the National Academy of
Sciences, USA 84: 7024±7027.
See also: Plasmids; Topoisomerases
DNA Synthesis
J Read and S Brenner
Copyright ß 2001 Academic Press
doi: 10.1006/rwgn.2001.1861
DNA synthesis is the process whereby deoxynucleic
acids (adenine, thymine, cytosine, and guanine) are
linked together to form DNA. In vivo, most DNA
synthesis occurs as a result of DNA replication but
nucleotides can also be incorporated into DNA pre-
cursors during repair mechanisms and retroviruses are
able to synthesize DNA from viral RNA of virus-
infected cells.
DNA replication is initiated by the melting of the
DNA double helix. Further, local unwinding is cata-
lyzed by the enzyme helicase, which generates regions
of single-stranded DNA. The DNA is then primed by
the addition of short RNA sequences that provide an
initial 30 hydroxyl group to which deoxynucleotides
can be added. These primers are later removed. The
extension of nucleotide primers requires a group of
enzymes called DNA polymerases. Escherichia coli
contains DNA polymerases I, II, and III, polymerase
III being important for DNA the de novo synthesis of
new DNA strands and polymerase I for editing out
unpaired strands at the end of the growing strands.
The homologous enzymes in animals are polymerases
a, b, and g, with a being responsible for nuclear DNA
synthesis and g for mitochondrial DNA synthesis.
DNA polymerases extend DNA precursors by adding
nucleotides, one at a time, to the 30 end of an RNA/
DNA precursor. This results in the formation of phos-
phodiester bonds between the 50 phosphate group of
one nucleic acid to the 30 hydroxyl group of the next.
The type of nucleotide added at each point is deter-
mined by Watson±Crick base pairing with the tem-
plate DNA strand. The efficiency of this process is
improved by the 30 ±50 endonuclease activity of DNA
polymerases I and II which provides a postsynthetic
proofreading mechanism. However, since daughter
DNA strands must be synthesized on both strands
of the parent DNA, the replication enzymes must
move in the 50 ±30 direction on one strand and the 30 ±
50 direction on the other. This problem is solved by
synthesizing the leading strand in the 50 ±30 direction in
a continuous manner and the lagging strand in the 30 ±
50 direction through the synthesis of short, 50 ±30 Oka-
zaki fragments of DNA. These Okazaki fragments are
then connected by the enzyme DNA ligase to form a
continuous strand. Thus this mode of DNA synthesis
is known as semidiscontinuous replication.
DNA can also be synthesized by reverse transcrip-
tion. This is the mechanism whereby linear duplex
DNA is synthesized from a viral RNA precursor in
the cytoplasm of virus-infected cells, a process that
requires the enzyme reverse transcriptase. Reverse
transcription is a useful tool for synthesizing DNA
from mRNA precursors in vitro. During this process,
an oligonucleotide primer is annealed to the poly(A)
tail of the template mRNA. The primer is then
extended by the 50 ±30 stepwise addition of nucleotides
through the action of reverse transcriptase. The pro-
duct is a DNA±RNA hybrid, which can be converted
into a cDNA by treatment with RNAse and subse-
quent treatment with DNA polymerase I.
See also: DNA Ligases; DNA Polymerases; DNA
Structure; Okazaki Fragment; Replication;
Reverse Transcription
Dobzhansky, Theodosius
R C Lewontin
Copyright ß 2001 Academic Press
doi: 10.1006/rwgn.2001.0373
Theodosius Dobzhansky (1900±1975) was responsible
for the present understanding of the evolutionary sig-
nificance of genetic variation within and between popu-
lations. His experimental and observational work on
the genetics of natural populations, and the general-
izations that he made from those observations, estab-
lished the agendas that still characterize experimental