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CELL CYCLE

Cell division is the process by which cells reproduce. It allows an increase in cell number, or multiplication of cell. Thus, cell division is also cell multiplication. A unicellular organism divides and forms new
individuals while a multicellular organism result from division of the zygote. Cell division comes in two way, Mitosis or Meiosis. It starts with Interphase with checkpoints in the different stages monitor cell division
ensuring its smooth process. Cell cycle checkpoints normally ensure that DNA replication and mitosis occur only when conditions are favorable and the process is working correctly. The cell cycle control system is
driven by a built-in clock that can be adjusted by external stimuli (i.e., chemical messages). Checkpoints acts as a critical control point in the cell cycle where “stop” and “go ahead” signals can regulate the cell cycle.

What triggers the cell to divide?

Cell biologist have observed that the size of a cell seems to be a factor that stimulates its division. When a cell grows, its surface area expands more slowly than its volume does. Thus, eventually become
disproportionately large in comparison with the surface area. The surface area is not large enough to allow necessary amount of nutrients to enter the cell and to allow wastes to pass out. Therefore, as the surface-
to-volume ratio becomes relatively small, the cell may divide.

MITOSIS
Mitosis is the division of the cell nucleus in which he chromosomes in the parent cell divide into 2 identical sets. In the human body, mitosis is the process by which the number of cells is increased without changing
the information contained in the DNA or the amount of DNA which are called Somatic Cells. In unicellular organisms, such as yeast, mitosis is the means of reproduction. All offspring contain the same DNA and
hence contain the same genetic information.

INTERPHASE
PHASE PRCOCESS CHECKPOINT FUNCTION OF CHECKPOINT NOTES
INTERPHASE G1 Phase  Synthesis of mRNA and  G1 DNA  Evaluates the integrity of the  DNA damage is due to the accumulation of P53 protein that can trigger cell cycle
(Gap1) protein. Damage DNA arrest of apoptosis
 mRNA is the template for Checkpoint  Apoptosis means programmed cell death
protein synthesis.  P53 Proteins are tumor suppressing proteins that help in regulating the cell
 Ribosomes composed of RNA cycle.
and protein are the site for  DNA that are beyond repair cannot go to the next process.
protein synthesis.  Mutations in genes that encode cell cycle proteins can lead to unregulated growth,
 Remember: DNA makes RNA. resulting to tumor formation and ultimately invasion of cancerous cells to other
RNA in turn makes proteins organs.
 The cell doubles in size,  Restrictive  Evaluates the cells capability  If the cell receives a “go ahead” signal, it can proceed to S Phase.
enzymes, and organelles. DNA to undergo cell division  If not, it will exit the cell cycle and switch to a non-dividing state called G0 or
Mitochondria and ribosomes Checkpoint  Ensures that the cell is large Resting Phase
roughly doubled in number enough to divide and that  Resting Phase is a period in the cell cycle in which cells exist in an inactive, non-
enough nutrients are cycling state.
available to support the
resulting daughter cells
PHASE PRCOCESS CHECKPOINT FUNCTION OF CHECKPOINT NOTES
INTERPHASE G1 Phase  Restrictive  Cells in G0 are called:
(Gap1) DNA Quiescent- dormant
Checkpoint - reversible
Cont’d… Cont’d… Senescent- aging or deteriorating
Cont’d… - irreversible
 Quiescent Cells may go back to cell division with proper stimulus
 Senescent cells aged or deteriorate due to DNA damage.
S Phase  Chromosomes are replicated  S DNA  Monitors the replication  Each Chromosome consists of two identical parts called chromatid. The two
(Synthesis) which means that there is Damage process during Synthesis chromatids are often called sister chromatids.
twice the DNA now present in Checkpoint Phase.  Chromosomes are DNA and histones in a coiled form that can be seen as a rod-
the cell. shaped structure.
 Histones are highly alkaline protein molecules.
 Chromosomes will become visible only in the Prophase during Mitosis Proper.
During the S Phase, chromosomes cannot be seen in an ordinary light microscope.

G2 Phase  The cell rapidly grows and  G2 DNA  Checks the activity in G2 to
(Gap 2) protein synthesis continues. Damage ensure its proper flow.
 The cell is prepared for Checkpoint
mitosis and necessary  Unreplicated  Ensures that DNA replication
enzymes and structures are DNA is complete before proceeding .
formed. Checkpoint to mitosis.

MITOSIS PROPER
PHASE PRCOCESS CHECKPOINT FUNCTION OF CHECKPOINT NOTES
MITOSIS PROPER Prophase  Sub divided into 3 steps NONE  EARLY PROPHASE
(please see notes)
- Chromatin coils and forms chromosomes. In this stage, chromosomes
condense and are now visible
- Simultaneously both the nucleolus and the nuclear membrane break down
and disappear.
- In organisms other than plants, two dark spots appear next to the
disappearing nucleus. These small cylindrical bodies are called Centrioles.
- These centrioles move away from each other, going towards the opposite
ends or poles of the cell.

MITOSIS PROPER
PHASE PRCOCESS CHECKPOINT FUNCTION OF CHECKPOINT NOTES
MITOSIS PROPER Prophase  MIDDLE PROPHASE
- Development of spindle fiber occurs.
Cont’d Cont’d - There are 2 types of spindle fibers
1. Polar Fibers- extends across the cell from centriole to centriole
2. Kinetochore Fibers- extends from the centromeres f a chromosome to the
centrioles. It controls the movements of the chromosome.
Centromere is the region of a chromosome to which the microtubules of the
spindle attach.

 LATE PROPHASE
- The 3rd fiber is formed.
3. Astral Fibers – those that grow and radiates from each centriole.
Metaphase  Kinetochore fiber directs the Spindle  Guarantees the proper
chromosomes to the center of Assembly alignment of the
the cell in an area called Checkpoint chromosomes at the
Metaphase Plate or Metaphase Plate.
Equatorial Plate.  Ensures that all of the
 Once in place in the equator chromosomes are attached to
of the cell, the chromosome is the spindle fiber
held in the center by the  This prevents the untimely
Kinetochore fibers. onset of anaphase.
Anaphase  Consist of 2 Substages:  The movement of the chromosomes in this phase is rapid and dramatic.
1. Anaphase A  Plant cell rarely have Anaphase B
- Kinetochore fiber separates  Sometimes Anaphase A happens before Anaphase B and vice versa
and move the sister  In this phase, Cytokinesis starts to occur and continues to the next phase.
chromatids towards the  Cytokinesis- is the process of dividing the cytoplasm in half.
opposite poles
2. Anaphase B
- The Polar fiber begin to
elongate while the Astral
fiber pull them on the other
side.
- These results in the poles
moving farther apart from
each other.

MITOSIS PROPER
PHASE PRCOCESS CHECKPOINT FUNCTION OF CHECKPOINT NOTES
MITOSIS PROPER Telophase  Two identical set of Chromosome  Prevents the  In animal cell, the cleavage furrow is produced when the contractile ring, which is
chromatids are Segregation cytokinesis to start made up of protein, constrict the middle of the cell. The constriction continues
Cont’d clustered at the Checkpoint until all chromosomes until the opposite surface of the cell membrane are in contact and finally form the
opposite sides of the are correctly separated. 2 daughter cells.
cell.  In plant cell, the walls are strong and cannot be constricted so there is no
 Chromosomes uncoils cleavage furrow that can be observed. Instead, cell plate forms. The cell plate is
and both the nucleolus involved in forming the cell wall of each daughter cell in plants.
and the nuclear
envelop reappear.
 Cytokinesis continues
with the visible
appearance of the
cleavage furrow, a
groove on the animal
cell membrane
between the poles.
 Mitosis serves, any purposes. It ensures that the number of chromosomes of the parent cell is identical to its two daughter cells.

For example:
- Humans have 46 chromosomes in each cell in the diploid state. A diploid cell has two sets of chromosomes, each coming from the parent cell. So, if the parent cell has 46 chromosomes, then the two
daughter cells resulting from Mitosis will have 46 chromosomes also.
- In mosquito, there are 6 chromosomes in each cell in the diploid state so the daughter cells from mitosis will also have 6 chromosomes each.

 Mitosis also ensures he growth of the offspring.

For example:

- A human life starts life as a zygote, a fertilized egg. This zygote will undergo continuous mitotic division. All cells resulting from multiple cell division will make up the human body.
- We become taller because bone cells continue to undergo mitosis. As long as the epiphyseal plate in the bone can still undergo mitosis in the long bone, increase in height continue. When the long bone
can no longer undergo mitosis, the epiphyseal plate becomes the epiphyseal line.
- When a person reaches age of 18, mitosis resulting in bone elongation drastically decrease to almost no activity at all. This means that a significant increase in height will cease.

 Mitosis also replaces the damage cells in the wounds.


- The damage cells are replaced by new cells produced by healthy cells. The faster the healthy cells replace the damaged cells, the faster the healing process will be.

While Mitosis give benefits to the body, it can also cause problems if it happens too often. Located in chromosome 17 are P53 proteins. As mentioned earlier, P53 Proteins are tumor suppressing proteins
that can trigger cell cycle arrest or apoptosis. If P53 protein mutates, mitosis would not stop which may result in cancer.

MEIOSIS
Meiosis is the process of nuclear division that reduces the number of the chromosomes by half. This process of cell division is involved in sexual reproduction. This process of cell division is involved in sexual
reproduction where the number of chromosomes of diploid cells are reduced into halves, one for the sperm and the other for the egg turning them into haploid cells. So, when the egg and sperm unite, the normal
number of 46 chromosomes will be restored as a chromosomal number of one from the original set of 46 already had side effects. It is also during Meiosis where genetic variation takes place because of the
process called genetic recombination.

MEIOSIS
PHASE PROCESS
INTERPHASE Same with Mitosis Same with Mitosis
Meiosis 1 Prophase 1 Divided into 5 Stages:
1. Leptotene Stage
- DNA strands coil, shorten and thicken to form chromosomes.
2. Zygotene Stage
- Synapsis starts
- Synapsis is the close pairing of the homologous chromosomes. It is possible because of the
initial formation of the synaptonemal complex.
- Synaptonemal complex is a highly organized protein structure that connects the two
homologous chromosomes together. This structure is speculated to mediate chromosomes’
successful condensation, pairing, recombination, and crossing-over.
3. Pachytene Stage
- Synapsis is complete and crossing-over can take place.
- In crossing-over, non-sister chromatids in the homologous chromosomes exchange their
segments.
- This process increases genetic variations of the organism because different combinations of
exchange genetic material are allowed to happen.
4. Diplotene Stage
- The Synaptonemal Complex starts to dissolve and the homologous chromosomes starts to
separate in the process called Terminalization.
- Terminalization is the separation of the chromosome from the centromere towards the ends.
- However, in this stage, strands of DNA are still connected at the site of the exchange, forming
an X-shaped structure called Chiasma (plural: Chiasmata).
5. Diakinesis
- Homologous chromosomes continue to separate
- The homologous chromosomes condensed and shortened
- Terminalization of Chiasmata occurs
- Just like in Mitosis, the nucleolus and nuclear membrane disappear.
- The cell is now ready for Metaphase I
MEIOSIS
PHASE PROCESS
Meiosis 1 Metaphase 1  Homologous chromosomes move to Metaphase Plate or Equatorial Plate
 Some of the paternal and maternal chromosomes move towards one pole while the others move
Cont’d towards the other pole.
 This random movement or orientation of chromosomes is the basis of the principle of
independent assortment in genetics.

Anaphase 1  Homologous chromosomes separate


 Each chromosome still holds the sister chromatids. Some of these chromatids now contain the
segments of exchanged DNA from crossing-over.
 As in Mitosis, one chromosome of each pair is pulled by action of the spindle fiber to one pole of
the cell and the other is pulled to the opposite pole.
Telophase 1  Homologous chromosomes have reached the poles.
 The resulting cells have only half of the number of chromosomes. Chromosomes still have pairs of
attached chromatids.
 The nuclear membrane starts to reappear and cytokinesis will occur to complete the creation of
the two haploid daughter cells.
Meiosis II Note that the following process will be similar to Mitosis except that the daughter cells produced will have only half of their parent’s genetic material.
Prophase II  The chromosomes begin to condense
 The nuclear membrane and nucleolus disappear
 Spindle fiber begin to form
Metaphase II  Chromosomes align to the equatorial plate
 The kinetochores are then attached to the centrosome of each sister chromatids
 The sister chromatids prepare themselves to move to the opposite poles
Anaphase II  The sister chromatids begin to separate,
 Each chromatid moves to the opposite side of the poles
Telophase II  The chromosomes uncoil
 The nuclear membrane and the nucleolus reappear
 At this point, cytokinesis splits the cells, producing four haploid cells

 If the Anaphase I or II does not correctly separate the homologous chromosomes and their sister chromatids, nondisjunction happens.
 Non-disjunction is the failure to separate the homologous chromosomes which may have adverse effects depending on the chromosomes affected.
o Ex:
When chromosome 21 experience nondisjunction, the resulting consequence will be Down Syndrome. In Down Syndrome, there are 3 copies of chromosome 21 instead of just 2.
The 3 copies result when one sex cell with two copies of chromosome 21 meets with a normal sex cell with only one copy of chromosome 21.
Table 1: Comparison of Mitosis and Meiosis

Meiosis Mitosis
1. Requires two nuclear divisions 1. Requires one nuclear division
2. Chromosomes synapse and cross over 2. Chromosomes do not synapse nor cross over
3. Centromeres survive Anaphase I 3. Centromeres dissolve in mitotic anaphase
4. Halves chromosome number 4. Preserves chromosome number
5. Produces four daughter nuclei 5. Produces two daughter nuclei
6. Produces daughter cells genetically different from parent and each other 6. Produces daughter cells genetically identical to parent and to each other
7. Used only for sexual reproduction 7. Used for asexual reproduction and growth

Table 2: Meiosis compared to Mitosis


Meiosis I compared to Mitosis Meiosis II compared to Mitosis
Meiosis I Mitosis Meiosis II Mitosis
Prophase I Prophase Prophase II Prophase
Pairing of homologous No pairing of No pairing of No pairing of
chromosomes Chromosomes chromosomes chromosomes
Metaphase I Metaphase Metaphase II Metaphase
Bivalents at metaphase plate Duplicated chromosomes at metaphase plate Haploid number of duplicated chromosomes at Diploid number of duplicated chromosomes at
metaphase plate metaphase plate
Anaphase I Anaphase Anaphase II Anaphase
Homologues of each bivalent separate and Sister chromatids separate, becoming Sister chromatids separate, becoming daughter Sister chromatids separate, becoming daughter
duplicated chromosomes move to poles Daughter chromosomes that move to the poles chromosomes that move to the poles chromosomes that move to the poles

Telophase I Telophase Telophase II Telophase


Two haploid daughter cells not identical to Two diploid daughter cells, Four haploid daughter cells not genetically Two diploid daughter cells,
the parent cell identical to the parent cell identical identical to the parent cell

DIFFERENT CHROMOSOMAL DISORDERS

Cri du chat syndrome, also known as chromosome 5p deletion syndrome, 5p− (said minus) syndrome or
Lejeune's syndrome, is a rare genetic disorder due to a missing part (deletion) of chromosome 5. Its name is a French
term (cat-cry or call of the cat) referring to the characteristic cat-like cry of affected children.

Cri-du-chat (cat's cry) syndrome, also known as 5p- (5p minus) syndrome, is a chromosomal condition that results when
a piece of chromosome 5 is missing. Infants with this condition often have a high-pitched cry that sounds like that of a cat.

Klinefelter syndrome is a genetic disorder that affects males. Klinefelter syndrome occurs when a boy is
born with one or more extra X chromosomes. Most males have one Y and one X chromosome. Having extra X
chromosomes can cause a male to have some physical traits unusual for males.
Klinefelter syndrome is a chromosomal condition that affects male physical and cognitive development. Its
signs and symptoms vary among affected individuals. Affected individuals typically have small testes that do
not produce as much testosterone as usual.
Tay–Sachs disease (also known as GM2 gangliosidosis or hexosaminidase A deficiency) is a rare autosomal
recessivegenetic disorder. In its most common variant (known as infantile Tay–Sachs disease), it causes a progressive
deterioration ofnerve cells and of mental and physical abilities that begins around 7 months of age and usually results in death
by the age of four. The disease occurs when harmful quantities of cell membrane components known
as gangliosides accumulate in the brain's nerve cells, eventually leading to the premature death of the cells. A ganglioside is a
form of sphingolipid, which makes Tay–Sachs disease a member of the sphingolipidoses. There is no known cure or treatment.

Sickle Cell Disease


The term sickle cell disease (SCD) describes a group of inherited red blood cell disorders. People with SCD have abnormal
hemoglobin, called hemoglobin S or sickle hemoglobin, in their red blood cells.
Hemoglobin is a protein in red blood cells that carries oxygen throughout the body.
“Inherited” means that the disease is passed by genes from parents to their children. SCD is not contagious. A person cannot
catch it, like a cold or infection, from someone else.
People who have SCD inherit two abnormal hemoglobin genes, one from each parent. In all forms of SCD, at least one of the
two abnormal genes causes a person’s body to make hemoglobin S. When a person has two hemoglobin S genes, Hemoglobin
SS, the disease is called sickle cell anemia. This is the most common and often most severe kind of SCD.

Turner syndrome is a chromosomal condition that affects development in females. The most common feature of Turner
syndrome is short stature, which becomes evident by about age 5. An early loss of ovarian function (ovarian hypofunction or
premature ovarian failure) is also very common. The ovaries develop normally at first, but egg cells (oocytes) usually die
prematurely and most ovarian tissue degenerates before birth. Many affected girls do not undergo puberty unless they receive
hormone therapy, and most are unable to conceive (infertile). A small percentage of females with Turner syndrome retain
normal ovarian function through young adulthood.
About 30 percent of females with Turner syndrome have extra folds of skin on the neck (webbed neck), a low hairline at the
back of the neck, puffiness or swelling (lymphedema) of the hands and feet, skeletal abnormalities, or kidney problems. One
third to one half of individuals with Turner syndrome are born with a heart defect, such as a narrowing of the large artery
leaving the heart (coarctation of the aorta) or abnormalities of the valve that connects the aorta with the heart (the aortic
valve). Complications associated with these heart defects can be life-threatening.
Most girls and women with Turner syndrome have normal intelligence. Developmental delays, nonverbal learning disabilities,
and behavioral problems are possible, although these characteristics vary among affected individuals.
Duchenne muscular dystrophy (DMD) is an X-linked recessive form of muscular dystrophy, affecting around 1 in 3,600
boys, which results in muscle degeneration and premature death. The disorder is caused by a mutation in the gene dystrophin,
located on the human X chromosome, which codes for the protein dystrophin.

Hemophilia
Hemophilia is a rare hereditary (inherited) bleeding disorder in which blood cannot clot normally at the site of a wound or injury. The disorder occurs because certain blood clotting factors are missing or do not
work properly. This can cause extended bleeding from a cut or wound.
PKU
Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the levels of a
substance called phenylalanine in the blood. Phenylalanine is a building block of proteins (an amino
acid) that is obtained through the diet. It is found in all proteins and in some artificial sweeteners.
Phenylketonuria (PKU) is a rare genetic condition that causes an amino acid called phenylalanine to
build up in the body. Amino acids are the building blocks of protein. Phenylalanine is found in all
proteins and some artificial sweeteners. Your body uses an enzyme called phenylalanine hydroxylase
to convert phenylalanine into tyrosine, a nonessential amino acid. Your body needs tyrosine to create
neurotransmitters, such as epinephrine, norepinephrine, and dopamine.
PKU is caused by a defect in the gene that helps create phenylalanine hydroxylase. When this enzyme
is missing, the body is unable to break down phenylalanine. This causes a buildup of phenylalanine in
the body. Early diagnosis and treatment can help relieve symptoms of PKU and prevent brain damage.

Other chromosome abnormalities:


• arise from errors in meiosis, usually meiosis I;
• occur more often during egg formation (90% of the time) than during sperm formation;
• become more frequent as a woman ages.
• Aneuploidy—is the presence of abnormal number of chromosomes in a cell. It is the most common chromosome abnormality. It is caused by non-disjunction, the failure of chromosomes to correctly separate:
- homologues during meiosis I or
- sister chromatids during meiosis II
- For example: a human cell having 45 or 47 chromosomes instead of the usual 4