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Cell Cycle or Cell-Division Cycle – Part 1

https://www
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com/watch?v=eqJqhA8HSJ0
https://www
...
com/watch?v=VLJF8Pf8spw

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Cell cycle
• Fundamental means by which all living things are propagated (reproduce)
• Cycle of duplication and division
• Series of events occurring in a cell between one division and the next
• Orderly sequence of events in which it duplicates its contents and then divides in two
• Replication is coordinated with cell cycle so that two copies of genome are available when the cell
divides
• A complex set of cytoplasmic and nuclear processes have to be coordinated with one another
during the cell cycle

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• In unicellular species, such as bacteria (prokaryote) and yeasts (lower eukaryote)
• Each cell division produces an additional organism

• In multicellular species
• Cell division produces a pair of genetically identical daughter cells
• Many rounds of cell division are required to make a new individual
• Cell division is needed in the adult body to replace cells that are lost by wear and tear or by
programmed cell death
• An adult human must manufacture many millions of new cells each second to maintain the
status quo
• If all cell division is halted, for example, by a large dose of ionizing radiation - the individual
will die within a few days

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Functions performed during cell cycle
• The most basic function of the cell cycle is to duplicate accurately the vast amount of DNA in the
chromosomes and then segregate the copies precisely into two genetically identical daughter
cells
• Discrete cell-cycle events occur against a background of continuous growth
• In addition to duplicating their genome, most cells also duplicate their other organelles and
macromolecules, otherwise they would get smaller with each division
• The vast majority of cells also double their mass and duplicate all their cytoplasmic organelles
• Total protein content of a typical cell increases more or less continuously throughout the cycle
• RNA synthesis continues at a steady rate, except during M phase, when the chromosomes
are apparently too condensed to allow transcription
• Purpose of cell cycle - passing on the genetic information to the next generation of cells
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• During embryonic growth and later development
• Cell division occurs in virtually every tissue
• In the adult organism
• Most tissues become quiescent
• A cell’s decision to divide or not is of crucial importance to the organism
• Internal and external cues trigger signalling pathways inside the cell that activate or inactivate a set
of core proteins that move the cell cycle forward

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• One of the properties that distinguishes various types of cells within a multicellular plant or animal is
their capacity to grow and divide
• Three broad categories of cells:
• Cells, such as muscle cells, nerve cells or red blood cells, that are highly specialized and lack
the ability to divide

• Once these cells have differentiated, they remain in that state until they die
• Cells that normally do not divide but can be induced to begin DNA synthesis and divide when
given an appropriate stimulus
• Liver cells, which can be induced to proliferate by the surgical removal of part of the liver
• Lymphocytes, which can be induced to proliferate by interaction with an appropriate antigen
• Cells that normally possess a relatively high level of mitotic activity
• Stem cells of various adult tissues, such as
• Hematopoietic stem cells that give rise to red and white blood cells
• Stem cells at the base of numerous epithelia that line the body cavities and the body surface
• The relatively unspecialized cells of apical meristems located near the tips of plant roots and
stems also exhibit rapid and continual cell division
• Stem cells retain their potential to divide and
to differentiate into any of a number of cell types
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Phases and Major Events of Cell Cycle

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Major events of cell cycle
• DNA replication
• DNA must be replicated
• Mitosis
• Replicated chromosomes must be segregated
into two separate cells
• Cytokinesis
• Cell divides into a pair of genetically identical
daughter cells

•

•

DNA duplication takes place in S phase and
occupies about half of the cell cycle time in a
typical mammalian cell
After S phase, chromosome segregation and cell
division occur in M phase, which requires much
less time (less than an hour in a mammalian cell)
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The cell-division cycle

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Phases of standard cell cycle
• G1, S, G2 and M are the traditional subdivisions of the standard cell cycle
• Most cell cycles conform to this standard scheme, however, there are exceptions

• Interphase
• Much longer part of the cycle is known as interphase
• Interphase comprises of G1, S, G2
• This period of continuous cell growth includes S phase, when DNA replication occurs, and two
gaps, the G1 and G2 phases, between S phase and M phase
• Mitosis
• During mitosis the replicated chromosomes are segregated into separate nuclei (by mitosis)
and the cell splits into two (by cytokinesis)

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G = Gap

The four successive phases of a standard eukaryotic cell cycle
• During interphase the cell grows continuously; during M (mitosis) phase it divides
• DNA replication is confined to the part of interphase known as S (synthesis) phase
• G1 phase is the gap between M phase and S phase
• G2 phase is the gap between S phase and M phase
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The eukaryotic
cycle

cell

• The durations (in
hours) of the four
stages vary

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• The details of cell cycle vary from organism to organism and at different times in an organism’s life
• Cell cycles can range in length
• The duration of the cell cycle varies greatly from one cell type to another
• Fly embryos have the shortest known cell cycles, each lasting as little as 8 minutes
• Their cell cycles lack both G1 and G2 phases
• Several months in slowly growing tissues, such as the mammalian liver
• Although the lengths of all phases of the cycle are variable to some extent, by far the greatest
variation, in most of the commonly studied types of cells, occurs in the duration of G1
• Almost all the variation in cell cycle length in the adult body occurs during the time the cell spends
in G1 or G0
• By contrast, the time taken for a cell to progress from the beginning of S phase through mitosis is
usually brief (typically 12-24 hours in mammals) and relatively constant, regardless of the interval
from one division to the next

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Four stages of cell cycle
• Cell division accompanying mitosis in eukaryotes occurs in four well-defined stages
• In the S (synthesis) phase, the DNA is replicated to produce copies for both daughter cells
• In the G1 and G2 phases (G indicates the gap between divisions), new proteins are synthesized
and the cell approximately doubles in size
• In the M phase (mitosis), the maternal nuclear envelope breaks down, paired chromosomes are
pulled to opposite poles of the cell, each set of daughter chromosomes is surrounded by a newly
formed nuclear envelope, and cytokinesis pinches the cell in half, producing two daughter cells

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Interphase
• Period between nuclear divisions
• Much longer part of the cycle
• Comprises of three phases - G1 S, G2
• DNA in the nucleus is replicated
• Chromosomes are in their extended form
• Cell grows (increases) in size
• Total protein content of a typical cell increases more or less continuously throughout the cycle
• RNA synthesis occurs (transcription occurs)
• Centrosome is duplicated (centrosome is duplicated in S phase)

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Gap phases (G for gap)
Serves following purposes
• Provide time for cell to prepare for next phase of cell cycle
• Example, prior to entry into S phase, most cells must reach a certain size and level of protein
synthesis to ensure that there will be adequate proteins and nutrients to complete the next
round of DNA synthesis
• To check that previous phase of cell cycle has been completed appropriately and provide
time to complete that step
• If there is a problem with a previous step in cell cycle, cell cycle checkpoints arrest the cell
cycle to provide time for the cell to complete that step
• Provide time for the cell to monitor the internal and external environment to ensure that
conditions are suitable and preparations are complete before the cell commits itself to the
major upheavals of S phase and mitosis
• Cell cycle arrests in these phases if conditions are not favorable for upcoming event
• In these phases cell cycle progression is regulated by various intra- and extra-cellular signals

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•

Provide additional time for growth
• If interphase lasted only long enough for DNA replication, the cell would not have time to
double its mass before it divided
• Otherwise cells would get smaller with each division

•

Act as time delays
• To give time for the damage to be repaired before the cell cycle continues
• To allow cell growth
• For the duplication of organelles
• To monitor the internal and external environment to ensure that conditions are suitable and
preparations are complete before the cell commits itself to the major upheavals of S phase and
mitosis
• For synthesis of RNA and proteins
• Most cells require much more time to grow and double their mass of proteins and
organelles than they require to replicate their DNA and divide
• Partly to allow more time for growth, extra gap phases are inserted in most cell cycles
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• Gap 1 or G1 phase
• First interval period
• Gap phase prior to DNA synthesis
• The interval between the completion of mitosis and the beginning of DNA synthesis
• An interval when transcription, translation and other cellular activities occur

• Cells with damaged DNA arrest cell cycle in G1 before DNA synthesis to prevent DNA synthesis
from occurring with damaged chromosomes
• The cell monitors its environment and its own size and, when the time is ripe, takes a decisive
step that commits it to DNA replication and completion of a division cycle

• Include common points from previous slides
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• Gap 2 or G2 phase
• Second interval period
• Gap phase between S and M phases
• The interval between the end of DNA synthesis and the beginning of mitosis
• Cells with damaged DNA arrest cell cycle in G2 phase before M to prevent mitosis from
occurring with damaged chromosomes
• The G2 phase provides a safety gap, allowing the cell to ensure that DNA replication is complete
before it plunges into mitosis
• Provides time for unreplicated DNA to complete replication

• Include common points from previous slides

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G0 (G zero) phase
• Specialized resting state or quiescent state
• Cells in G1, if they have not yet committed themselves to DNA replication, can pause in their progress
around the cycle and enter G0

• Cells may remain here for days, weeks, or even years before resuming proliferation
• With few exceptions, cells that have stopped dividing, whether temporarily or permanently, whether in
the body or in culture, are present in a stage preceding the initiation of DNA synthesis
• Cell cycle control system is either temporarily or permanently dismantled
• Cells that are arrested in this state, which includes the majority of cells in the body, are said to be in
the G0 state to distinguish them from the typical G1-phase cells that may soon enter S phase
• Almost all the variation in cell cycle length in the adult body occurs during the time the cell spends in
G1 or G0
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• A cell in G0 begins to divide again, when
• The conditions are favorable
• The cell receives a growth-promoting signal to proceed from G0 into G1 phase and thus re-enter
the cell cycle

• Cells in G0 can re-enter the division cycle through the G1 phase and hence resume proliferation

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• Most cells in our body are in G0, but the molecular basis and reversibility of this state vary in different
cell types
• Neurons and muscle cells are in a terminally differentiated G0 state
• In which their cell cycle control system is completely dismantled
• The expression of genes encoding various CdKs and cyclins are permanently turned off and
cell division never occurs
• Other cell types withdraw from cell cycle only transiently and retain the ability to reassemble the
cell cycle control system quickly and re-enter the cycle
• Most liver cells are in G0, but they can be stimulated to divide if the liver is damaged
• Some lymphocytes, withdraw from and re-enter the cell cycle repeatedly throughout their
lifetime (induced by antigen)

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S phase (S for synthesis)
• Replication of the nuclear DNA occurs in S phase to produce copies for both daughter cells
• It occupies about half of the cell cycle time in a typical mammalian cell

• Histones, which are required for the formation of new chromatin, are made at a high rate only in S
phase
• Centrosome is duplicated in S phase
• Some of the enzymes that manufacture deoxyribonucleotides and replicate DNA are synthesized in S
phase
• Replication process itself can be arrested under certain circumstances
• for e
...
, if DNA is damaged and must be repaired before copying can be completed
• Initiation of replication requires
• Phosphorylation of pre-RC (pre-replication complex) proteins
• e
...
, ORC (origin recognition complex), MCM2-7 (Minichromosome maintenance proteins),
Cdc6 (cell division cycle protein 6), Cdt1 (cell division cycle dependent transcript 1)
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M phase (Mitosis phase)
• After S phase, chromosome segregation and cell division occur in M phase
• It requires much less time (less than an hour in a mammalian cell)
• Period when nuclear and cell division occurs
• Nucleus and then the cell divide into two
• Initiation of mitosis requires
• Phosphorylation of proteins that control
• Chromosome condensation
• Nuclear envelope breakdown
• Spindle assembly

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Series of events occurring during M phase
• Chromosome condensation
• The duplicated DNA strands, packaged into elongated chromosomes, condense into the much
more compact chromosomes required for their segregation
• Nuclear envelope breaks down
• Cell's microtubules reorganize to form the mitotic spindle
• Replicated chromosomes, each consisting of a pair of sister chromatids, become attached to the
microtubules of the mitotic spindle
• During metaphase, chromosomes are aligned at the equator of the mitotic spindle, poised for
segregation
• Sudden separation of sister chromatids marks the beginning of anaphase
• Paired chromosomes are pulled to opposite poles of the spindle
• Chromosomes move to opposite poles of the spindle, where they decondense
• Each set of daughter chromosomes is surrounded by a newly formed nuclear envelope
• The cell is then pinched into two by cytoplasmic division or cytokinesis and cell division is complete
• Cytokinesis pinches the cell in half, producing two daughter
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