Biology Reference
In-Depth Information
chromosomes become visible in mitosis or meiosis. DNA replication occurs at a
rate of up to 1000 nt/second (
Dixon 2009
).
The
cell division cycle
consists of five distinct phases, if interphase is included.
Nondividing cells are in interphase, the longest phase. Some cells remain in
interphase and never divide. However, if cell division occurs, the chromosomes
must be replicated in a precise manner, and any errors in replication must be
detected and, ideally, corrected. There are two
gap phases
or periods (G
1
and
G
2
), when the cell is carrying out its normal metabolic activities (
Figure 1.14
),
separated by the
S phase
, when DNA replication or synthesis occurs.
Mitosis
(M)
occurs subsequent to the G
2
phase (also known as the premitotic phase). Mitosis
occurs when highly condensed duplicated chromosomes separate and segregate
into daughter cells followed by cytokinesis in which the cell membrane forms
around each daughter cell. During the G
2
phase, cells grow rapidly and pro-
teins and RNAs are synthesized. Mitosis is divided into several phases (prophase,
metaphase, anaphase, and telophase), as described in Chapter 3.
To reduce the amount of time required to replicate the very long DNA mol-
ecule in eukaryotic chromosomes, DNA replication is initiated at a series of
rep-
lication origins
≈
40kb apart on the linear chromosome and proceeds in both
directions (
Figures 1.11, 1.12
) (
DePamphilis 1999
). For example, replication in
D. melanogaster
occurs at a rate of
≈
2600 nt pairs/minute at 24 °C. The largest
chromosome in
Drosophila
is
≈
8
×
10
7
nt long, so, with
≈
8500 replication origins/
chromosome,
≈
0.25-0.5 hour is required to replicate this chromosome. If replica-
tion occurred from a single replication fork, rather than from multiple replica-
tion origins, replication of a single chromosome would require
≈
15 days.
Origins of replication of eukaryotic chromosomes are recognized by a pro-
tein complex called the Origin of Replication Complex (ORC) that is essential for
initiation of DNA replication at yeast origins. The protein complex opens the
DNA, stabilizes the single-stranded DNA that is formed, and allows polymerases
to copy the DNA. The ORC complex seems to recruit other proteins (including
DNA helicases) to the origin of replication, leading to the start of replication.
Proteins related to yeast ORC proteins have been identified in
Drosophila
and
other eukaryotes (
Gavin et al. 1995
).
Eukaryotes contain several different DNA polymerases (
Hubscher et al. 2002
).
One DNA polymerase is located in the mitochondria and is responsible for rep-
lication of mitochondrial DNA. The other DNA polymerases are in the nucleus
and are involved in DNA replication, repair, and recombination. Polymerase
α
complexes with
primase
(the RNA polymerase that primes DNA synthesis) and
seems to function with primase to synthesize short RNA-DNA fragments. Two
other polymerases then synthesize the leading and lagging strands, extending
