Cell cycle (prokaryotic), genetic regulation of WORLD OF MICROBIOLOGY AND IMMUNOLOGY108•
varies among species but in somatic cells, it occurs through
the equal division of the cytoplasmatic content, with the
plasma membrane forming inwardly a deep cleft that ulti-
mately divides the parental cell in two new daughter cells.
The identification and detailed understanding of the
many molecules involved in the cell cycle controls and intra-
cellular signal transductionis presently under investigation by
several research groups around the world. This knowledge is
crucial to the development of new anti-cancer drugs as well as
to new treatments for other genetic diseases, in which a gene
over expression or deregulation may be causing either a
chronic or an acute disease, or the impairment of a vital organ
function. Scientists predict that the next two decades will be
dedicated to the identification of gene products and their
respective function in the cellular microenvironment. This
new field of research is termed proteomics.See also Cell cycle (Prokaryotic) genetic regulation of;
Genetic regulation of eukaryotic cells; Genetic regulation of
prokaryotic cellsCELL CYCLE(PROKARYOTIC), GENETIC
REGULATION OFCell cycle (prokaryotic), genetic regulation ofAlthough prokaryotes do not have an organized nucleusand
other complex organelles found in eukaryotic cells, prokary-
otic organisms share some common features with eukaryotes
as far as cell division is concerned. For example, they both
replicate DNAin a semi conservative manner, and the segrega-
tion of the newly formed DNA molecules occurs before the
cell division takes place through cytokinesis. Despite such
similarities, the prokaryotic genome is stored in a single DNA
molecule, whereas eukaryotes may contain a varied number of
DNA molecules, specific to each species, seen in the interpha-
sic nucleus as chromosomes. Prokaryotic cells also differ in
other ways from eukaryotic cells. Prokaryotes do not have
cytoskeleton and the DNA is not condensed during mitosis.
The prokaryote chromosomes do not present histones, the
complexes of histonic proteins that help to pack eukaryotic
DNA into a condensate state. Prokaryotic DNA has one single
promoter site that initiates replication, whereas eukaryotic
DNA has multiple promoter sites. Prokaryotes have a lack of
spindle apparatus (or microtubules), which are essential struc-
tures for chromosome segregation in eukaryotic cells. In
prokaryotes, there are no membranes and organelles dividing
the cytosol in different compartments. Although two or more
DNA molecules may be present in a given prokaryotic cell,
they are genetically identical. They may contain one extra cir-
cular strand of genes known as plasmid, much smaller than the
genomic DNA, and plasmidsmay be transferred to another
prokaryote through bacterial conjugation, a process known as
horizontal genetransfer.
The prokaryotic method of reproduction is asexual and
is termed binary fission because one cell is divided in two new
identical cells. Some prokaryotes also have a plasmid. Genes
in plasmidsare extra-chromosomal genes and can either beseparately duplicated by a class of gene known as trans-
posonsType II, or simply passed on to another individual.
Transposons Type I may transfer and insert one or more genes
from the plasmid to the cell DNA or vice-versa causing muta-
tion through genetic recombination. The chromosome is
attached to a region of the internal side of the membrane,
forming a nucleoide. Some bacterial cells do present two or
more nucleoides, but the genes they contain are identical.
The prokaryotic cell cycleis usually a fast process and
may occur every 20 minutes in favorable conditions.
However, some bacteria, such as Mycobacterium leprae(the
cause of leprosy), take 12 days to accomplish replication in
the host’s leprous lesion. Replication of prokaryotic DNA, as
well as of eukaryotic DNA, is a semi- conservative process,
which means that each newly synthesized strand is paired with
its complementary parental strand. Each daughter cell, there-
fore, receives a double-stranded circular DNA molecule that is
formed by a new strand is paired with an old strand.
The cell cycle is regulated by genes encoding products
(i.e., enzymesand proteins) that play crucial roles in the main-
tenance of an orderly sequence of events that ensures that each
resultant daughter cell will inherit the same amount of genetic
information. Cell induction into proliferation and DNA repli-
cation are controlled by specific gene products, such as
enzyme DNA polymerase III, that binds to a promoter region
in the circular DNA, initiating its replication. However, DNA
polymerase requires the presence of a pre-existing strand of
DNA, which serves as a template, as well as RNAprimers, to
initiate the polymerization of a new strand. Before replication
starts, timidine-H^3 , (a DNA precursor) is added to a Y-shaped
site where the double helices were separated, known as the
replicating fork. The DNA strands are separated by enzyme
helicases and kept apart during replication by single strand
proteins (or ss DNA-binding proteins) that binds to DNA,
while the enzyme topoisomerase further unwinds and elon-
gates the two strands to undo the circular ring.
DNA polymerase always makes the new strand by start-
ing from the extremity 5’ and terminating at the extremity 3’.
Moreover, the two DNA strands have opposite directions (i.e.,
they keep an anti-parallel arrangement to each other).
Therefore, the new strand 5’ to 3’ that is complementary to the
old strand 3’ to 5’ is synthesized in a continuous process (lead-
ing strand synthesis), whereas the other new strand (3’ to 5’)
is synthesized in several isolated fragments (lagging strand
synthesis) that will be later bound together to form the whole
strand. The new 3’ to 5’ strand is complementary to the old 5’
to 3’. However, the lagging fragments, known as Okazaki’s
fragments, are individually synthesized in the direction 5’ to 3’
by DNA polymerase III. RNA polymerases produce the RNA
primers that help DNA polymerases to synthesize the leading
strand. Nevertheless, the small fragments of the lagging strand
have as primers a special RNA that is synthesized by another
enzyme, the primase. Enzyme topoisomerase III does the
proofreading of the newly transcribed sequences and elimi-
nates those wrongly transcribed, before DNA synthesis may
continue. RNA primers are removed from the newly synthe-
sized sequences by ribonuclease H. Polymerase I fills the gaps
and DNA ligase joins the lagging strands.womi_C 5/6/03 2:04 PM Page 108