CYTOGENETICS 02/05/2021 INTERPHASE

CELL DIVISION

Importance of Cell Division

Cell division is an important event that is involved in:
 Growth and development
o Zygote to adulthood – as a zygote has to
undergo a series of division until the
organism is fully developed/adulthood
 Repair in wounds
 Cell replacement in certain tissues
o Erythrocytes must be replaced –  Cells appear to be quiet and the nuclei are
erythrocytes have a certain half-life so featureless
probably 21 days, it should be replaced  This is the phase of the cell cycle where the cell
constantly performs its normal activities for life
 Interphase is not a stage of mitosis I
 Nucleus (if any) is still visible
 Nuclear envelops clearly visible
 Chromatin – a DNA wrapped around the histones
which has not condensed yet; NO BISIBLE
CHROMOSOMES yet

THE CELL CYCLE

- cycle of events describing the cell’s preparation for
division, and division itself
Three stages:
 Interphase – the period between cell divisions
 Mitosis – involves nuclear division
 Cytokinesis – involves cytoplasmic division  Interphase undergoes 3 or 4 phases:
o Gap 0 – we include the first one
 Also called G0 phase
 Quiescent
 Cells are resting but
metabolically active
 Soon after division, the daughter
cell enters G1 and exits to G0
this happens when the cell has to
rest and will not divide again in
the near future
 There are cells that remain in this
phase for life, however there are
cells that re-enter G1 from G0
o Gap 1
 Intensive metabolic activity
 Many genes active
  RNA and proteins are
synthesized
 Cell increases in size – result of
intensive metabolic activity such
as the synthesis of RNA and
proteins
 Prepares for cell division and
DNA replication
 It is the gap between the cell
division
o S-phase  Prophase
 DNA synthesis o The double stranded chromosomes are
 Produce sister chromatids able to move freely around the cytoplasm
 S stands for synthesis o No nucleus that encloses these
 Involves DNA replication that chromosomes
produces the sister chromatids
o Gap 2
 Finish many metabolic processes
that are required for division
 Cell must be at the right size
during interphase and DNA
should be replicated
 Followed by cell division
o Mitosis
o Cytokinesis  Transition to metaphase
– THEN CYCLE IS REPEATED – o In preparation for metaphase, spindle
apparatus/fibers would form from the
MITOSIS centrioles
 A process of cell duplication in which one cell o This spindle fiber will attach to the
divides into two genetically identical daughter chromosomes
cells

STAGES OF MITOSIS
 Early Prophase
o DNA begins to condense
o Centrioles also appear

 Metaphase
o Meta = MIDDLE
o Chromosomes line up at the spindle
equator/middle of the cell
o Chromatids are attached to the spindle
fibers

 Late Prophase
o Centrioles will migrate to opposite poles
o Spindle fibers form
o Nuclear envelope begins to disintegrate
and dissolve
o New nucleoli also dissolve
 Anaphase
o Sister chromatids move apart/pulled
toward each pole by the spindle fiber
o ANA =AWAY
o Centromere divides at this point so that
each chromatid would still have its own
centromere

THIS IS THE SUMMARY OF MITOSIS

 Telophase
o Nuclear division occurs
o Chromosomes are now enclosed in
nuclear membrane (Chromosomes re-
appear)
o Chromosomes are no longer condensed
Chromosomes diffuse
o Mitotic spindle dissolves
o Nuclear membrane forms
o New nucleoli form
o Opposite of what happens in prophase

Cell prepares for mitosis during interphase, wherein the

DNA duplicates, the cell enlarges, then it enters prophase,
followed by metaphase, anaphase, telophase and finally
division through cytokinesis

CONTROL OF THE CELL CYCLE

 It is essential that daughter cells produced be
exact duplicates of the parent cell
 Remember that in mitosis, the daughter cells are
 CYTOKINESIS exactly alike, genetically identical
o Cytoplasm divides; division of  Mistakes in the duplication or distribution of
cytoplasm that results in the formation of the chromosomes lead to mutations that may be
two daughter cells passed forward to every new cell produced from
o After mitosis, two diploid daughter cells an abnormal cell
have formed  It is important that the chromosomes are
o Begins with the formation of a cell replicated exactly or precisely without errors and
furrow, which forms at a location of the the chromosomes are distributed to the daughter
metaphase plate through the contraction cells equally
of a ring of microtubules called the  To prevent this, checkpoints exist within the cell
contractile ring cycle. Checkpoints ensure that everything goes
right
 These checkpoints are points in the cell cycle
where progress through the cycle can be halted
  until conditions are suitable for the cell to G1/S (Restriction)  end of cell cycle’s
proceed to the next stage G1, before S phase
 inspects for DNA
 there are three checkpoints:
damage (ex:
o G1 Checkpoint – cell must prepare for exposure to UV
duplication of DNA so this checkpoint if: light) before
 Cell size is adequate replication
 Nutrient availability is sufficient  cell size and
 Growth factors (signals from adequacy of
other cells) are present nutrients
 Once it is passed, it will go to S- G2/M  end of G2
phase for DNA triggering the start
replication/synthesis of mitotic phase
o G2 Checkpoint – before it enters  inspects replicated
mitosis, this is another checkpoint DNA for damage,
 Checks the cell size if it is sufficient nutrients,
adequate growth factors
 Chromosome replication is M (Metaphase)  during metaphase
successfully completed  checks if
 If everything is ok, then mitosis chromosomes are
properly aligned
will begin
along the
o Metaphase Checkpoint metaphase plate
 Checks whether all the  important for equal
chromosomes are attached to distribution of
mitotic spindle chromosomes to
 If there’s a chromosome that is the daughter cells
not attached to the mitotic
spindle, then mitosis will be REGULATION OF THE CELL CYCLE
halted  Proteins that control the cell cycle (cyclin-
CDK complexes)
\ o Cyclin
 forms a complex with CDK
o Cyclin-dependent kinases (CDK)
 phosphorylate specific targets in
the checkpoint
 is a kinase/enzyme that adds
phosphate groups to targets

o Each CDK must bind with appropriate

cyclin in order to be activated
o These two proteins have to form a
complex in order for the CDK to be
activated
o It must bind with appropriate cyclin to be
activated: D cyclins, E and A cyclins, and
B cyclins *check table above*
What happens if the checkpoint mechanisms detect
problems with the DNA? (ex: stalled or damaged
replication fork / double strand break)
 the cell cycle is halted (Cell Cycle Arrest)
 the cell attempts to either complete DNA
replication or repair the damaged DNA
 if damage is irreparable, the cell may undergo
apoptosis, or programmed death/cell suicide
 the most important aspect of the cell cycle that is
being monitored by the check point is the DNA
because there should be no damage or changes in
the DNA
FAILURE OF CHECKPOINTS
Causes:
 Mutation
 Genomic arrangements resulting in genetic
instability (birth defects, disease, cancer)
o Ex: if one chromosome did not attach in
spindle fiber, that chromosome would be
lost during division; loss of chromosome
may result in monosomy that could lead
to genetic instability
ADDITIONAL REGULATORS OF THE CELL
CYCLE
 Tumor suppressor proteins
o halt the cell cycle
o best known tumor suppressor proteins:
 p53 – refers to the molecular
mass and molecular mass/weight
of the protein in kilo Dalton (p
for protein 53 Kilo Dalton
 p21 – p for protein, 21 for Kilo
Dalton
 retinoblastoma (Rb) protein
o ex: p53 protein detects DNA damage and
stops cell cycle in G1 by blocking CDK2
activity and recruit enzymes to repair the
DNA
o if damage cannot be repaired, p53
triggers apoptosis or cell suicide
o a mutation leads to uncontrolled cell
division (common in cancer), or
production of defective cells
_____________________________________________
CELL DIVISION
 MITOSIS – Somatic cells
o Product: 2 daughter cells (genetically
identical)
o Diploid cells- 46 chromosomes
 MEIOSIS – Gametes
o When: Gametogenesis
o Product: 4 daughter cells (genetically
unique)
o Haploid cells – 23 chromosomes
_____________________________________________
MEIOSIS
Why do gametes have to be haploid?
 Fertilization involves the fusion of a sperm and
egg to form a zygote
 A zygote is a fertilized egg
 Egg has 23 chromosomes and sperm has 23
chromosomes then you’ll have a zygote that has
46 chromosomes
 If egg and sperm is diploid, egg has 46, sperm
has 46, zygote will have 92 chromosomes which
is incompatible with life
MEIOSIS DEFINED
 Sex cells develop from germ cells, which are
diploid
 Ovum and sperm production
 In meiosis, the chromosome number is reduced
 The cellular events are very similar to mitosis,
except for the number of chromosomes produced
in each daughter cells
 Divided into two phases Meiosis I and II
  Diploid cell divides to two, then divide to four,  Sub stages:
and will have a daughter cell of 4 o Leptotene
 chromosomes condense and
INTERPHASE IN MEIOSIS become visible but the sister
 There is also chromatids are not very visible
duplication of but already in the condense form
chromosome forming o Zygotene
sister chromatids for  Involves the pairing of
each chromosome homologous chromosome
during interphase  Blue chromosome and red
 Similar to mitosis chromosome in the picture
interphase would now pair and form a
 Chromosomes synapsis that will attach along
replicate S-phase their length
 Each duplicated chromosome consist of two  This attachment starts from the
identical sister chromatids attached at their telomere
centromeres  A synaptonemal complex would
 Centriole pairs also replicate be formed between these two
chromosomes
MEIOSIS I
 Homologous
chromosomes
segregate in two
daughter cells
 the chromosomes
received by the
daughter cells are still in the form of dyads (with
two sister chromatids)
 the basis for segregation of alleles in Mendel’s
Law of Segregation

MEIOSIS I: PROPHASE 1
 different from the prophase in mitosis
 parent cell is germ cell
 centrioles appear and the chromosomes
condensed the nuclear envelope will also
disappear

Bivalent chromosome = homologs are attached (4

chromatids: tetrad)
o Pachytene
 Crossing over occurs
 Sister chromatids are visible
 Later, the synaptonemal
complex dissociates
 The synapsis is complete
 Two chromosomes are attached
from one telomere to the other
telomere
  This ensures that allele pairs of which is the maroon and light violet would exchange
the two chromosomes are paired which results in variation among the offspring with
with each other regards to their traits which creates diversity of the traits
 Because of synapsis, of offspring. That is why, even if you have the same father
chromosomes are said to be and mother, the siblings would be non-identical because
bivalent; two chromosomes by of this phenomenon of crossing over
two chromosomes and each
chromosomes has 2 sister MEIOSIS I: METAPHASE I
chromatids and therefore there
are 4 chromatids in a bivalent
called TETRAD
o Diplotene
 The homologous chromosomes
are joined together by a chiasma
o Daiakinesis
 Chromosomes become fully
condensed; nuclear envelope
disappears; spindle fibers attach
the chromosomes, ready for
metaphase

 Shortest phase
 During metaphase I, the bivalents (paired
homolog) align along the metaphase plate
 Aligned in the metaphase plate are paired
homologs which are bivalent

PACHYTENE: CROSSING OVER DURING

MEIOSIS
This figure shows what is independent assortment

 The orientation of homologous pairs at the

 In crossing over, non-sister chromatids exchange
segments
Ex: dark purple chromatid would exchange segments of
the chromosome with this orange chromatid of the other
chromosome and then the other non-sister chromatid
metaphase plate is random during metaphase I
 Possibilities in orientation: B1 on left or B1 on
right along vice versa
 When this segregate, A1 and B1 will go together
in one cell and A2 and B2 will go together in one
 cell or it could be the one in the right side of the  Each pole now has haploid set of chromosomes
picture: 4 possible variations  Two daughter nuclei form
 Causes further variation  Distribution of chromosome in the two poles of
 Formula 2𝑛 = 4 the cell enclosed in a nucleus
Then n = 2 (number of chromosomes)  Nuclear membrane reforms
Thus 22 = 4 combinations  Two nuclei
 Thus, variations among individuals are due to:  Cytokinesis occurs and two haploid daughter
o Crossing-over cells are formed
o Independent assortment o each of two daughter cells from meiosis I
enters meiosis II
MEIOSIS I: ANAPHASE I  Division of nucleus followed by cytokinesis
o Cell will again contract and will divide
into two daughter cells that has haploid
and the homologues have separated but
the chromosomes are still dyad

MEIOSIS II
 No interphase II
o Very short – no more DNA replication
 The homologous chromosomes segregate, with  Remember: Meiosis II is similar to mitosis
one chromosome from each bivalent migrating to
each pole (disjunction- disjoin) MEIOSIS II: PROPHASE II
 Sister chromatids remain attached at their
centromeres
 Chromosomes are pulled apart from each other
towards opposite poles
 Separation of homologous chromosomes; not the
sister chromatids
 Sister chromatids are still attached at the
centromere

MEIOSIS I: TELOPHASE I

 Same as prophase in mitosis

MEIOSIS II: METAPHASE II
 Same as telophase in mitosis
 Nuclei form
 Nuclear membrane forms
 Cytokinesis occurs
 REMEMBER:
o Four haploid daughter cells (either sperm
or egg) produced
o Gametes = sperm or egg

 Same as metaphase in mitosis

 Dyads are on the metaphase plate

MEIOSIS II: ANAPHASE II

Division of cells that would result in the formation of

female sex cells: ovum and the male sex cells:
spermatozoa/sperm
 Meiosis in females is called: oogenesis
o Mother cell: oognonium
 Diploid
 There are two chromosomes of
 Same as anaphase in mitosis each kind
 Sister chromatids separate o Father cell: Spermatogonium
 Chromosomes are pulled apart towards their own  There would be an Interphase where the cells
poles/opposite poles of the cell would enlarge and the chromosomes would be
replicated which will give you dyads (before
MEIOSIS II: TELOPHASE II meiosis I)
 As meiosis I occurs, resulting in the formation of
two daughter cells for the:
o Oogenesis:
 Secondary Oocyte
 Daughter of primary
oocyte
 One large oocyte is
formed and one is small
cell which is referred to
as polar body
 Unequal size of cells
occurs
o Spermatogenesis
 Secondary Spermatocyte
  Cells are of the same  That ootid/oocyte would go to
sizes which are: haploid the menstrual blood
but still has dyads;  In males, spermatogenesis starts at puberty so
sister chromatids are before puberty, they do not produce sperm
still joined by a  After puberty, spermatogenesis will keep on
centromere for each occurring through the lifetime of the male
chromosome
 Followed by Meiosis II
o Oogenesis
 Four cells are formed
 Unequal cytokinesis where the
polar body divides into two and
the secondary oocyte divide into
two also but one is smaller polar
body and one big ootid
 Ootid will further develop and
mature to turn into an Ovum
o Spermatogenesis
 Cells are of equal sizes; equal
cytokinesis which would mature
into Spermatozoa/Sperms This shows how fertilization occurs
 Note that: the chromosomes after Meiosis II are  When a sperm fertilizes an egg, the sperm’s
no longer dyads but monads acrosomal enzymes digest the egg’s jelly coat
 In females, oogenesis starts in embryonic stage then proteins on the sperm head bind to
and it stops at prophase I: before birth receptors of the egg and that results in the fusion
o Before a female is born, oogenesis stops of the sperm plasma membrane and the egg
at prophase I plasma membrane and only the sperm nucleus
o The primary oocyte would remain at this enters the egg. Egg nucleus will now fuse with
form for 12-40 years the sperm nucleus and you will have a Zygote
o And you will associate that with this nucleus; a fertilized egg
number years, for the reproductive  Why is the egg very big:?
years of a female; indicating that at that o Because the only contribution of the
age, the egg is only at prophase I male to the zygote is its nucleus
o It will continue with meiosis I at puberty o The content of the cytoplasm of the
or after puberty sperm does not go into the egg
 Each secondary oocyte would  What nurtures the zygote?
mature or would continue o It’s the egg
meiosis up to metaphase II; o That’s why there’s a very big cytoplasm
which once again, stops at for the egg because the egg is the one
metaphase II that gives nutrient to the Zygote
o Meiosis II is only completed only after o That’s why mother’s cytoplasm has a
fertilization great influence to the growth of zygote
o Usually one egg is only released every  Remember that Meiosis II is only completed
month when fertilization occurs
 When we ovulate every month,
our egg cell is only at
metaphase II only
 It would only continue to
complete meiosis II when it is
fertilized by a sperm
o If there is no fertilization:
Meiosis is not a cycle unlike mitosis. Meiosis is a process
in which a diploid cell divides itself into 4 haploid cell.
The diagram shows meiosis as a non-cyclic process.
 In mitosis: once the cells have divided, those cells
will perform other functions and the resulting
cells will no longer divide
 In meiosis: fertilization occur and zygote is
formed

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