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Cellular Reproduction
I
GENE 330
The Cell Cycle and DNA replication in
Eukaryotes
• Although cell division occurs in all organisms, it takes place
differently in prokaryotes and eukaryotes.
• In a population of dividing cells , each cell passes through a series
of defined stages, which constitutes the cell cycle.
• The cell cycle can be divided into two major phases based on
cellular activities: M phase and Interphase.
• M phase includes 1. process of mitosis (duplicated chromosomes
are separated into two nuclei), and 2. cytokinesis (the cell divides
into two daughter cells).
• Interphase is a period between cell divisions (cell grows and is
engages in metabolic activities).
The Cell Cycle
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In order for an organism to grow, 3 events must take place:
1. The cell mass must increase
2. There must be a duplication of the genetic material
3. A division process must occur so that each daughter cell
receives an equal and identical complement of the genetic
material
These occurrences take place in an ordered progression of
events during the cell’s life span, or cell cycle
Cell Cycles in Vivo
• One of the properties that distinguishes various types of cells within
a multicellular animal or plant is their capacity to grow and divide.
• We can accept three broad categories of cells:
1. Cell, such as nerve cells, muscle cells, or red blood cells,
that are highly specialized and lack the ability to divide.
2. cells, that normally do not divide but can be induced to begin
DNA synthesis and divide when given an appropriate stimulus
(liver cells, lymphocyte).
3. Cells that normally possess a relatively high level of mitotic
activity (spermatogonia, hematopoietic stem cells, cells of apical
meristems).
• Cell cycles can range in length from as short as 30 minutes in a
cleaving frog embryo, whose cell cycles lack both G1 and G2
phases, to several month in slowly growing tissues (mammalian
liver).
• With a few exception, cell that have stopped dividing (temporarily or
permanently) in the culture or in the body, are present in a stage
preceding the initiation of DNA synthesis. Cell are in the Go state.
• The cell must generate an internal signal to proceed from Go or G1
into S phase.
• Once the signal to begin DNA replication has been generated, the
cell invariably completes that round of DNA synthesis and continues
through mitosis.
The Cell cycle
• Definition – The sum total of the division related events that occur
between the time a cell completes one cell division, and the time it
completes the next one.
• 2 basic elements of a cell cycle :
– Genetic material in both the nucleus and the organelles must
replicate completely, and 1 copy must end up in each of the
daughter cells : nuclear division
– Cytoplasmic material and membranes must arrange so that there
will be two/more complete cells to receive this information :
cytokinesis
The Cell Cycle
• A typical eukaryotic cell cycle can arbitrarily begin in what is called the
G1 phase . At this point, the cell contain two copies of each
chromosome (C2 -the normal diploid state of eukaryotic cell).
• Sometimes late in G1 phase synthesis of histones is one of the first
indications of incipient DNA replication.
• The cell then enters synthesis, or S phase. During this stage, the DNA
is replicated and the histones and nonhistone proteins are deposit on
the daughter DNA molecules to reproduce the chromatin structure.
• When replication is complete, the cell enters what is called the second
gap phase or G2 phase. It has a DNA content four times the haploid
amount (C4). In most eukaryotic cells, the total time required for G1, S,
and G2 phases is many hours.
• In the interphase, the chromatin is dispersed throughout the nucleus
and is actively engaged in transcription.
• At the end of G2, the cell is ready to enter the process called mitosis,
during which it divides.
The eukaryotic cell cycle. Changes in the amount of DNA (blue line)
and rate of histone synthesis (red line) with time during two cell
cycles. The DNA content is measured in units of the haploid genome
(C). The time scale is typical of many eukaryotic cells.
The Cell Cycle
• The M phase, or the division phase, is the final part of the cell cycle.
• This phase contains the different stages of mitosis e.g. prophase,
metaphase, anaphase and telophase.
• In prophase , the replicated chromosomes condense into the typical
methaphase chromosome structures. The nuclear membrane
disintegrates, and the mitotic spindle forms. The spindle consists
of contractile microtubules that pull pairs of chromatids apart so that
the daughter cells each receive identical sets of chromosomes. In
telophase the nuclear membrane then re-forms about each
daughter nucleus, and the cell itself divides.
• This cellular division is called cytokinesis.
• After division , the chromosomes of the daughter cells decondense ,
and a new G1 phase begins.
• The 2 daughter cells are identical to each other and to the parent
cell.
Mitosis
The Cell Cycle
• Cells can leave the mitotic cell cycle at the G1 to the following two
condition
– In many tissues of higher organisms, the G1 phase becomes
very prolonged after growth and tissue differentiation is
complete. The most extreme examples are nerve cells. Such
nondividing cells are in permanently arrested G1 phase, which is
often called G0 phase.
– cells can further develop to reproduction cells (gametes and
spores) by entering meiosis.
The cell cycle trigers
• The key process, that triggers the successive stages in the cell cycle
appears to be phosphorylation of a number of nuclear proteins, and
the key enzymes are a set of kinases. Its activation was found to
require assotian with specific small proteins called cyclins.
• There exist several cyclin-dependent kinases and number of cyclins
to associate with them.
• Each transition in the cell cycle appears to have unique
cyclin/kinase complex as trigger.
• A somewhat simplified view of the roles of these proteins in
mammalian cells is shown in next Figure.
The cyclin-dependent kinase CDK2 is involved in the entrance to S phase, and
cdc2, with cyclins A and B, regulate mitosis. Cdc2 is phosphorylated at entry to
G2, but must be dephosphorylated for mitosis to commence. In this somewhat
oversimplified figure, is indication of CDK2 and cyclins E and A (CE,CA) in
triggering S phase, the role of cdc2 and its phosphorylation at the S/G2
boundary, and the participation of cyclins A(CA) and B(CB) in the entry to
mitosis.
Replication of the DNA
• The basic mechanisms of DNA replication are quite similar in
eukaryotes and prokaryotes. The enzymology is not fundamentally
different.
• In both cases, replication is semiconservative and is continuous on
one strand and discontinuous on the other.
• As in prokaryotes, eukaryotic replication on the retrograde arm
entails assembly of short RNA primer molecules, elongation from
the primers by a DNA polymerase, and ligation of Okazaki
fragments.
• A significant difference in eukaryotic and prokaryotic DNA replication
is the size of the Okazaki fragments. They are much smaller in
eukaryotes (only 135 bases long, or about the size of the DNA on a
nucleosome).
• Eukaryotic cells contain five DNA polymerases.
• Three of these – α,δ, and ε – are used during S phase replication.