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Cell division

Dr. Subeer
Introduction
 The cell cycle is an ordered series of events
involving cell growth and cell division that
produces two new daughter cells.
 A cell has a life cycle extending from one

division to the next.


 The cell cycle has two major phases:

1. Interphase
2. Mitotic phase
Cont
 During interphase, the cell grows and DNA is
replicated.
 During the mitotic phase, the replicated DNA

and cytoplasmic contents are separated and


the cell divides.
Diagram
Interphase
 During interphase, the cell undergoes normal
processes while also preparing for cell
division.
 The three stages of interphase are

1. G1 (or Gap one) phase

2. S (synthesis phase) phase


3. G2 (Gap 2) phase
G1 Phase
 is an interval between cell division and DNA
replication.
 During this time, a cell synthesizes proteins

and grows.
 they accumulate the materials needed in the

next phase to replicate their DNA.


S Phase
 a cell carries out DNA replication.
 Each of its DNA molecules uncoils into two

separate strands, and each strand acts as a


template for the synthesis of the missing
strand.
G2 Phase
 Is a brief interval between DNA replication
and cell division.
 In G2, a cell finishes replicating its centrioles

and synthesizes enzymes that control cell


division.
 May be additional cell growth during G .
2
 The final preparations for the mitotic phase
must be completed before the cell is able to
enter the first stage of mitosis.
Length of cell cycle
 The length of the cell cycle varies greatly
from one cell type to another.
 Cultured connective tissue cells called

fibroblasts divide about once a day and spend


8 to 10 hours in G1, 6 to 8 hours in S, 4 to 6
hours in G2, and 1 to 2 hours in M.
 Stomach and skin cells divide rapidly, bone

and cartilage cells slowly, and skeletal muscle


and nerve cells not at all.
Cont
 Some cells leave the cell cycle for a “rest” and
cease to divide for days, years, or the rest of
one’s life.
 Such cells are said to be in the G0 (G-zero)
phase.
 The balance between cells that are actively
cycling and those standing by in G0 is an
important factor in determining the number of
cells in the body.
 An inability to stop cycling and enter G0 is
characteristic of cancer cells.
Mitotic (M) phase
 is the period in which a cell replicates its
nucleus, divides its DNA into two identical
sets (one per nucleus), and pinches in two to
form two genetically identical daughter cells.
 Mitosis phase include:

a. Mitosis (karyokinesis): nuclear division


• Daughter chromosomes distributed in two
daughter nuclei.
b. Cytokinesis: cytoplasm division
• Results in two genetically identical daughter cells.
Diagram
Cell division
 Cells divide by two mechanisms called
mitosis and meiosis.
 Meiosis: the production of eggs and sperm
 Mitosis serves all the other functions of cell

division: its importance


◦ the development of an individual from a one-celled
fertilized egg
◦ continued growth of all the organs after birth
◦ the replacement of cells that die
◦ the repair of damaged tissues.
Mitosis
 Has four phases
1. Prophase
2. Metaphase
3. Anaphase
4. Telophase
Prophase
 Chromosomes condense
 Nuclear envelope breaks down.
 Spindle fibers grow from centrioles.
 Centrioles migrate to opposite poles of cell.

 Metaphase
 Chromosomes lie along midline of cell.
 Some spindle fibers attach to kinetochores.
 Fibers of aster attach to plasma membrane.
Anaphase
 Centromeres divide in two.
 Spindle fibers pull sister chromatids to
opposite poles of cell.
 Each pole (future daughter cell) now has an
identical set of genes.
 Telophase
 Chromosomes gather at each pole of cell.
 Chromatin decondenses.
 New nuclear envelope appears at each pole.
 New nucleoli appear in each nucleus.
 Mitotic spindle vanishes.
Cont
Cont
 Telophase is the end of nuclear division.
 Cytokinesis division of the cytoplasm, begins in
anaphase and extends through the end of
telophase.
 It is achieved by the motor protein myosin
pulling on microfilaments of actin in the
membrane skeleton.
 This creates a crease called the cleavage furrow
around the equator of the cell, and the cell
eventually pinches in two.
 Interphase has now begun for these new cells.
Results of mitosis
 Two daughter nuclei
 Each with same
chromosome number
as parent cell (2n)
 Genetically identical to
each other and the
parent cell

Results: 2 daughter cells Diagram


Meiosis
 Formation of gametes ( egg and sperm)
 Called reduction-division.
 Preceded by interphase which includes

chromosome replication.
 Two meiotic divisions

◦ Meiosis 1 and meiosis 2


 Original cell is diploid (2n)
 Four daughter cells produced that are haploid

(n).
Importance of meiosis
 Two haploid (1n) gametes are brought
together thru fertilization to form a diploid
(2n) zygote.
 Meiosis must reduce the chromosome

number by half.
 Fertilization then restores the 2n number
Meiosis 1
 Early prophase I
 Chromatin condenses to form visible
chromosomes;
 each chromosome has 2 chromatids joined by a
centromere.
 Mid- to late prophase I
 Homologous chromosomes form pairs called
tetrads.
 Chromatids often break and exchange segments
(crossing-over).
 Centrioles produce spindle fibers.
 Nuclear envelope disintegrates.
Metaphase 1
 Tetrads align on equatorial plane of cell with
centromeres attached to spindle fibers.

 Anaphase I
 Homologous chromosomes separate and migrate
to opposite poles of the cell.
 Telophase I
 New nuclear envelopes form around chromosome
 cell undergoes cytoplasmic division (cytokinesis).
 Each cell is now haploid.
Meiosis 2
 Prophase II
 Nuclear envelopes disintegrate again
 chromosomes still consist of 2 chromatids.
 New spindle forms.

 Metaphase II
 Chromosomes align on equatorial plane.
Cont
 Anaphase II
 Centromeres divide
 sister chromatids migrate to opposite poles

of cell.
 Each chromatid now constitutes a single-

stranded chromosome.
 Telophase II
 New nuclear envelopes form around

chromosomes
 chromosomes uncoil and become less visible
 cytoplasm divides.
Cont
Control of the Cell Cycle
 Throughout the cell cycle, there are various
quality control check points which function to
ensure that various cellular conditions are met
before proceeding to the next phase of the
cycle.
 The timing of events in the cell cycle is

controlled by mechanisms that are both internal


and external to the cell.
 These quality control check points are carried

out by a family of proteins called cyclins and


cyclin dependent kinases (CDKs).
Cont
 1. Intracellular control of the cell cycle
◦ Positive: cyclins and CDKs
◦ Negative: RB and P53

 2. Extracellular control of the cell cycle


◦ A. mitogens
◦ B. growth factors
◦ C. survival factors
Regulation of the Cell Cycle by
External factors
 Both the initiation and inhibition of cell division
are triggered by events external to the cell when
it is about to begin the replication process.
 A lack of HGH can inhibit cell division, resulting
in dwarfism.
 Crowding of cells can also inhibit cell division.
Another factor that can initiate cell division is
the size of the cell; as a cell grows, it becomes
inefficient due to its decreasing surface-to-
volume ratio. The solution to this problem is to
divide.
Cyclins
 They are proteins which binds to enzymes
called cyclin dependent kinase (CDK).
 Cyclins are called cyclins because their

concentration and expression cycles


throughout cell cycle.
 Many types of cyclins exist which bind to

different types of CDKs.


Diagram
Cyclin dependent kinases (CDKs)
 CDKs are enzymes which activate the proteins
required for progression through cell cycle
and its check points.
 CDKs achieve this by phosphorylating certain

domains on target proteins.


 For CDKs to complete this function, they

must first interact with cyclins to form a


cyclin-CDK complex.
Cell cycle check points
1. G1 check point
2. G2 check point
3. M check point (spindle check point)
G1 check point
 This is the check point at which cells choose
whether to proceed with S phase and not to
divide and instead go into quiescence via the
G0 phase
 Checks for cell size, nutrients, growth factor,

DNA damage.
 This check point is mediated by the cyclin

E/CDK2 complex and two cell cycle regulator


proteins called retinoblastoma protein (RB)
and E2F
The G2 check point
 To make sure that cell division goes smoothly
the cell has an additional checkpoint before
M phase, called the G2 checkpoint.
 Checks for: DNA damage, DNA replication

completeness.
 If errors or damage of the DNA are detected,

the cell will pause at the G2 check point to


allow for repairs.
 If the damage is irreparable, the cell will

undergo apoptosis.
The spindle check point
 The M checkpoint is also known as the spindle
checkpoint.
 the cell examines whether all the sister

chromatids are correctly attached to the


spindle microtubules.
 the cycle will not proceed until all the

chromosomes are firmly attached to at least two


spindle fibers from opposite poles of the cell.
Diagram
Retiniblastoma protein (RB)
 The primary function of RB is to prevent
excessive cell division by inhibiting cell cycle
progression.
 When the appropriate signals for cell division

are present (i.e. cyclins) RB is inactivated by


phosphorylation.
 RB is normally bound to a transcription factor

called E2F. E2F is then able to bind the


promotors of proteins required for cell
division.
Tumor suppressor genes
 TSG code for proteins which function to
control cell division and ensure that it only
occurs when necessary.
 Mutations which lead to loss of function of

TSG increases the risk of cancer by increasing


the risk of uncontrolled cell division.
P53 (the guardian of the genome)
 The most important tumor suppressor gene
 P53 ensures that only cells free of DNA errors

can undergo cell division.


 If a cell contains DNA errors , P53 will either

arrest cell division until the DNA has been


repaired or it will trigger apoptosis of that
cell.
 Loss of P53 leads to accumulation of DNA

mutations and eventually cancer.

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