Chapter 3
Cells: The Living Units
97
3
DNA Replication
Before a cell can divide, its DNA must be
replicated exactly, so that identical copies of the cell’s genes can
be passed to each of its offspring. During the S phase, replica-
tion begins simultaneously on several chromatin threads and
continues until all the DNA has been replicated.
Human DNA molecules are very long. Replication of a DNA
molecule begins at several
origins of replication
along its length
that have a specific nucleotide sequence, a strategy that greatly
increases the speed of replication.
Replication is still being studied but appears to involve sev-
eral events:
1.
Enzymes attach to origins of replication and separate the
DNA strands so that
replication bubbles
form. At each end
of a replication bubble is a Y-shaped area, a
replication
fork
, where the helical parental DNA strands are being un-
wound
(Figure 3.32)
.
2.
Once the bubbles are formed, the parental DNA strands
are ready to serve as templates for making complemen-
tary DNA strands from free DNA precursors dissolved in
the nucleoplasm (Figure 3.32). However, there is a prob-
lem here because the
polymerase enzymes
that synthesize
DNA cannot start a new DNA strand from scratch. Tey
can only add new nucleotides to a strand that already
exists. Tis problem is solved by formation of a short,
complementary
RNA primer
, about 10 bases long, by a
primase enzyme
.
3.
Continuing from the primer, the enzyme
DNA polymer-
ase
positions complementary nucleotides along the tem-
plate strand and then covalently links them together. DNA
polymerase works only in one direction. Consequently,
one strand, the
leading strand
, is synthesized continu-
ously once primed, following the movement of the rep-
lication fork. Te other strand, called the
lagging strand
,
is constructed in segments in the opposite direction and
requires that a primer initiate replication of each segment.
4.
Ligase enzymes splice the short segments of DNA to-
gether. Eventually DNA polymerases replace the primers
with DNA nucleotides.
Te end result is that two DNA molecules are formed from the
original DNA helix (the template strands) and are identical to
it. Because each new molecule consists of one old and one new
nucleotide strand, this mechanism of DNA replication is called
semiconservative replication
(Figure 3.32).
As soon as replication ends, histones (synthesized in the
cytoplasm and imported into the nucleus) associate with the
DNA, completing the formation of two new chromatin strands.
Te chromatin strands, united by a buttonlike centromere (a
stretch of repetitive DNA), remain held together by the centro-
mere and a protein complex called
cohesin
, until the cell enters
the anaphase stage of mitotic cell division (see p. 101). Tey are
then distributed to the daughter cells as described next, ensur-
ing that each cell has identical genetic information.
Te progression from DNA replication into cell division pre-
sumes that the newly synthesized DNA is not damaged in any
way. If damage occurs, the cell cycle stops until the DNA repair
mechanism has fixed the problem.
Interp
hase
G
1
Growth
S
Growth and DNA
synthesis
G
2
Growth and final
preparations for
division
Anaphase
Metaphase
Prophase
Telophase
Cytokinesis
M
Mitotic
phas
e
(M
)
G
2
checkpoint
G
1
checkpoint
(restriction point)
Mit
os
is
Figure 3.31
The cell cycle.
During G
1
, cells grow rapidly and carry
out their routine functions. The S phase is the period of DNA syn-
thesis. In G
2
, materials needed for cell division are synthesized and
growth continues. During the M phase (cell division), mitosis and
cytokinesis occur, producing two daughter cells. Important check-
points at which mitosis may be prevented from occurring are found
throughout interphase; the diagram shows two.
G
1
(gap 1 subphase):
Te cell is metabolically active, synthesiz-
ing proteins rapidly and growing vigorously (Figure 3.31, light
green area). Tis is the most variable phase in terms of length.
In cells that divide rapidly, G
1
typically lasts several minutes to
hours, but in those that divide slowly, G
1
may last for days or
even years. Cells that permanently cease dividing are said to be
in the
G
0
phase
. For most of G
1
, virtually no activities directly
related to cell division occur. However, as G
1
ends, the centri-
oles start to replicate in preparation for cell division.
S phase:
DNA is replicated, ensuring that the two future cells
being created will receive identical copies of the genetic ma-
terial (Figure 3.31, blue area). New histones are made and as-
sembled into chromatin. One thing is sure, without a proper
S phase, there can be no correct mitotic phase. (We will de-
scribe DNA replication next.)
G
2
(gap 2 subphase):
Te final phase of interphase is brief
(Figure 3.31, dark green area). Enzymes and other proteins
needed for division are synthesized and moved to their
proper sites. By the end of G
2
, centriole replication (begun in
G
1
) is complete. Te cell is now ready to divide. Troughout
S and G
2
, the cell continues to grow and carries on with busi-
ness as usual.
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