CLINICAL CASES
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preceding Okazaki fragment. The RNA primer on the previous Okazaki
fragment is removed, the gap filled in with DNA and the strands ligated.
Oncogene: Genes whose products are involved in the transformation of
normal cells to tumor cells. Most oncogenes are mutant forms of normal
genes (protooncogenes).
Primase: An RNA polymerase that synthesizes a short RNA primer com-
plementary to a DNA template strand that is being replicated. This RNA
primer serves as the starting point for addition of nucleotides in the
replication of the strand serving as a template.
Recombination: Any process in which DNA strands are cleaved and
rejoined resulting in an exchange of material between molecules of DNA.
Tumor suppressor genes: Genes that encode for proteins that normally
inhibit the progress of a cell through the cell cycle. If these genes are
mutated, a deficiency in the suppressor proteins creates unregulated cell
growth, a condition permissive for tumorigenesis.
D ISC U SSIO N
DNA replication normally occurs during the S phase of the cell cycle. DNA
replication occurs in a semiconservative fashion and this is because of the intrin-
sic antiparallel nature of the double helix. All known DNA polymerases syn-
thesize DNA in a 5' to 3' direction; this means that one strand will be
continuously synthesized and the other must be made through a discontinuous
mechanism and the production of Okazaki fragments. After this process is
finished, the cell will divide the newly replicated material in mitosis. In some
aberrant cases, the cell will replicate its DNA over and over again without per-
forming an intervening mitosis. This generates cells with abnormally high con-
tent of DNA, an abnormal form of DNA replication control.
DNA replication begins by separating the parental DNA strands. This
is accomplished by enzymes called helicases. They separate the strands and
move along the strands in a fixed direction at the expense of ATP, opening up
the strands so that the DNA polymerases can bind to them. To prevent
reannealing of the two strands, single-stranded binding proteins bind the two
complementary strands. The next step in the replication process is the lay-
ing down of an RNA primer, which is catalyzed by the enzyme primase.
DNA polymerases extend the chain by adding deoxyribonucleotides to the
5' end of the RNA primer. It does this in a continuous fashion on the lead-
ing strand, but for the lagging strand, the one with its 5' end toward the
replication fork, a series of short segments termed Okazaki fragments
must be synthesized. The RNA primers of the Okazaki fragments are
removed as the DNA polymerase reaches the previous Okazaki fragment and
the DNA segments are then joined by DNA ligase.
DNA mutations arise from a variety of intrinsic and extrinsic factors.
Our genome is constantly under the assault of various genotoxic agents such
as ionizing radiation, oxygen free radicals, and UV light. These agents
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