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U N I T 1
Cell and Tissue Function
division involved in gamete (i.e., ovum and sperm) for-
mation, the fertilization process, and the mitotic cell
divisions involved in the formation of a new organism
from the single-celled fertilized ovum called the
zygote
.
Although genes have gotten a lot of attention, it is the
proteins that the genes encode that make up the major-
ity of cellular structures and contribute to their func-
tion. Proteins are responsible for the functional diversity
of cells, they perform most biologic functions, and it is
at their level that many regulatory processes take place,
many disease processes occur, and most drug targets are
found. The term
proteome
is a relatively new term, cre-
ated to define the complete set of proteins encoded by
a genome.
Proteomics,
the study of the proteome, uses
highly sophisticated technologic methods to examine
the molecular and biochemical events in a cell.
DNA Structure and Function
The DNA molecule that stores the genetic information in
the nucleus is a long, double-stranded, helical structure.
Deoxyribonucleic acid is composed of
nucleotides
, which
consist of phosphoric acid, a five-carbon sugar called
deoxyribose
, and one of four nitrogenous bases. These
nitrogenous bases carry the genetic information and are
divided into two groups: the
pyrimidine bases
, thymine
(T) and cytosine (C), which have one nitrogen ring; and
the
purine bases
, adenine (A) and guanine (G), which have
two. The backbone of DNA consists of alternating groups
of sugar and phosphoric acid, with the paired bases pro-
jecting inward from the sides of the sugar molecule.
Double Helix and Base Pairing
The native structure of DNA, as elucidated by James
Watson and Frances Crick in 1953, is that of a spiral
staircase, with the paired bases representing the steps
(Fig. 5-1). A precise complementary pairing of purine
and pyrimidine bases occurs in the double-stranded
DNA molecule in which A is paired with T and G is
paired with C. Each nucleotide in a pair is on one strand
of the DNA molecule, with the bases on opposite DNA
strands bound together by hydrogen bonds that are
extremely stable under normal conditions. The double-
stranded structure of DNA molecules allows them to
replicate precisely by separation of the two strands, fol-
lowed by synthesis of two new complementary strands.
Similarly, the base complementary pairing allows for
efficient and correct repair of damaged DNA molecules.
Several hundred to almost 1 million base pairs can
represent a gene, the size being proportional to the
protein product it encodes. Of the two DNA strands,
only one is used in transcribing the information for the
cell’s protein-building machinery. The genetic informa-
tion of one strand is meaningful and is used as a tem-
plate for transcription; the complementary code of
the other strand does not make sense and is ignored.
Both strands, however, are involved in DNA duplica-
tion. Before cell division, the two strands of the helix
separate and a complementary molecule is duplicated
next to each original strand. Two strands become four
strands. During mitotic cell division, the newly dupli-
cated double-stranded molecules are separated and
placed in each daughter cell by the mechanics of mitosis.
As a result, each of the daughter cells again contains the
meaningful strand and the complementary strand joined
together as a double helix. In 1958, Meselson and Stahl
characterized this replication of DNA as
semiconserva-
tive
replication, as opposed to
conservative
replication,
in which the parental strands reassociate when the two
strands are brought together (Fig. 5-2).
Although scientific discussion regarding the structure
and functioning of a gene goes into explicit detail, it does
not really address the question of what a gene is. Many
scientists are now in agreement that the proteins encoded
by DNA know no boundaries. This means that nucleo-
tides from one part of the genome can combine with
nucleotides from other regions at extreme distances on the
DNA molecule. It is also proposed that the functions of
some genes are controlled by regulatory regions, also at a
distance. Moreover, researchers now recognize that many
thousands of genes in the human genome do not code for
protein assembly, but rather for segments of ribonucleic
G
G
G
G
G
C
C
C
C
C
C
C
T
T
T
A
A
A
A
A
A
A
T
T
T
A
A
A
A
A
A
A
A
A
A
A
A
C
C
C
G
G
G
G
G
T
T
T
T
T
T
T
T
T
T
T
T
T
Replication
fork
Parental
strand
Parental
strand
New
strand
New
strand
FIGURE 5-1.
A replicating DNA helix.The parental strands
separate at the replication fork. Each parental strand serves as a
template for the synthesis of a new strand.The backbone of DNA
consists of a sugar–phosphate backbone with paired pyrimidine
bases (thymine [T] and cytosine [C] with their one nitrogen
ring) and purine bases (adenine [A] and guanine [G] with their
two nitrogen rings) projecting inward. (From Smith C, Marks
AD, Lieberman M. Marks’ Basic Medical Biochemistry. 2nd ed.
Philadelphia, PA: LippincottWilliams &Wilkins; 2005:222.)
