BIOLOGY 1

OUTLINE
6. The Cell Cycle
7. Cancer Biology
8. Stem Cells
THE CELL CYCLE
9. Asexual and Sexual
Repreoduction Cell division
● Constitutes the entire reproduction
of unicellular organisms
● Constitutes the growth and
development of multicellular
organisms
● Necessary for the maintenance and
repair of tissues

Mitosis
● Results in daughter cells with
identical genetic information

Meiosis
● Produces nonidentical daughter
cells (gametes) with haploid
chromosome count
○ Most eukaryotes are diploid
in their chromosome count

CHROMOSOME STRUCTURE
● Sister chromatids
● Centromere

Sister chromatids
● Each chromosome has 2 sister
chromatids
○ Ultimately counted as a
single chromosome as long
as held together by
centromere
○ Only counted as separate
chromosomes when
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separated during cell
division
● Each sister chromatid is an exact
copy of one another
○ Each chromatid is made of
chromatin fiber

Chromatin
● Made of DNA and associated
histone proteins
COMPONENTS OF THE CELL CYCLE
Nucleosome ● Mitotic phase (10%)
● Fundamental subunit of chromatin ○ Mitosis & cytokinesis
● Segment of 146 base pairs wrapped ● Interphase (90%)
around 8 histone proteins ○ Cell growth
○ Copying of chromosomes in
Solenoid preparation for cell division
● Secondary structure of chromatin
● Consists of 6 coiled nucleosomes
● Structure is supported by additional
histones

Centromere
● Constricted region of chromosomes
● Separates the chromosome into
short (p) and long (q) arms
PHASES OF MITOSIS
● Contains kinetochore proteins
1. Prophase
○ To attach to kinetochore
● Chromatin becomes more
microtubules during mitosis
tightly coiled
○ Condensed into
discrete
chromosomes
● Nucleoli disappear
● Mitotic spindle begins to
form
● Centrosomes move away
from one another
2. Prometaphase
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● Nuclear envelope fragments
● Microtubules extend from
each centrosome and invade
the nuclear area
● Chromosomes condense
further
● Kinetochore microtubules
attach to the centromere

3. Metaphase
● Chromosomes align at the
metaphase (equatorial) plate
● Centrosomes are at the
opposite poles of the cell
Mitotic spindle
● Chromosomes are at
● Microtubules & associated proteins
maximum condensation
that control chromosome
4. Anaphase
movement during mitosis
● Sister chromatids separate
○ Centrosomes, spindle
and move towards opposite
microtubules, asters
poles
● Assembly of spindle microtubules in
● Each chromatid becomes a
animal cells starts in the
full-fledged chromosome
centrosome
● Non-kinetochore
● Spindle microtubules include
microtubules leaven,
kinetochore & non-kinetochore
resulting in the elongation of
microtubules
the cell
● Asters - mcot that radiate from
5. Telophase
centros
● The nuclear envelope re-
forms
Asters
● Nucleoli reappear
● Microtubules that radiate from the
● Chromosomes become less
spindle pole
condensed
● Microtubules depolymerize
Non-kinetochore microtubules
● Also known as interpolar
microtubules
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● Results in 4 daughter cells

Cytokinesis
● Division of the cytoplasm
● Immediately follows telophase
● Constitutes the formation of the Homologous chromosomes
cleavage furrow in animal cells and ● Chromosomes duplicate during the
cell plate in plant cells S subphase of Interphase to form a
homologous pair
Cleavage furrow formation ○ The cell containing a
● Interaction between contractile ring homologous pair proceeds
of actin microfilaments and myosin with Meiosis I
results in a contraction ● Contain 1 set of chromosomes from
● As the border contracts, the each parent
cleavage furrow deepens until the ● Carry the same kinds of genes in the
parent cell is pinched into two same order
● DNA replication occurs in the
Cell plate formation Interphase before Meiosis I
● Vesicles from the golgi apparatus ● Separate during Meiosis I
move along the microtubules to the
middle of the cell during telophase
● Vesicles fuse, forming a cell plate

PHASES OF MEIOSIS
1. Meiosis I
● Reductional division
● From diploid to haploid
● Produces 2 daughter cells
2. Meiosis II PHASES OF MEIOSIS I
● Equational division 1. Prophase I
● Haploid count is retained ● Synapsis
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2. Metaphase I 1. Prophase II
● Homologous pairs are ● Mitotic spindle forms
arranged at the metaphase ● Chromosomes are now
plate composed of 2 sister
3. Anaphase I chromatids
● The separated homologous 2. Metaphase II
pair move towards opposite ● Chromosomes align at the
poles equatorial plate
4. Telophase I 3. Anaphase II
● Haploid daughter cells are ● Sister chromatids separate
produced and move towards opposite
● Cytokinesis follows poles
● In some species, nuclear 4. Telophase II
envelope re-forms and ● Nuclei form
chromosomes de-condense ● Chromosomes de-condense
● The resulting daughter cells
Synapsis are genetically different from
● Occurs during Prophase I one another and from the
● Homologous chromosomes are original parent cells
paired
● Chiasmata are formed
○ Cross-shaped structures
○ Indicate where crossing
over/recombination of DNA
will take place

Crossing over
● Exchange of segments between
non-sister chromatids
Cell Cycle control system
● Regulated by both internal and
external mechanisms
● Contain specific checkpoints where
the cell cycle stops until a go-ahead
signal is received

PHASES OF MEIOSIS II
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Cyclin
● Family of various proteins
PHASES OF INTERPHASE
● Activates Cdk by binding to it
1. 1st Gap (G1)
● Synthesizes during G2 subphase
● Most important checkpoint
for cells
Cyclin-dependent kinase (Cdk)
● Cell will usually complete
● Modify various protein substrates
the other subphases if this is
involved in the cell cycle
passed
● Must correlate substrates by
2. Synthesis (S)
transferring phosphate groups from
● Chromosomes are
ATP to specific amino acids in the
duplicated
substances
● DNA is synthesized
● Require the presence of cyclins to
3. 2nd Gap (G2)
become active
● Nuclear envelope is still
● Actively rises and falls with the
intact
concentration of cyclin
● One or more nucleoli are
○ Rises during S & G2
visible
○ Falls abruptly during M
● Centrosomes &
● When cyclin and Cdk are bound
chromosomes have
together, they form MPF
duplicated
● Chromosomes cannot be
Maturation-promoting factor (MPF)
seen individually since they
● Cyclin-Cdk complex
haven't condensed yet
● Triggers a cell’s passage past the
G2 checkpoint into the M subphase
➔ The cell grows during all 3 phases of
○ Upon the accumulation of
Interphase
enough MPF
● Promotes mitosis by
phosphorylating proteins
● Activity peaks during metaphase
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● Cycling of MPF is degraded during
anaphase Platelet-derived growth factor
○ Results in the termination of ● Made by mitogens
M subphase ○ Blood cell fragments
● Cyclin degradation continues as the ● Stimulate cell division by inhibiting
cell enters G1 subphase retinoblastoma protein
○ Cdk is recycled
Tumor suppressor proteins
➔ Signals registered at checkpoints ● Suppress the expression of genes
originate from internal surveillance that promote cell proliferation
mechanisms ● Bind to the transcription regulators
➔ Checkpoints also regulate external of particular genes
signals ● Control the rate of cell division and
apoptosis
G1 checkpoint ● Activated via phosphorylation by
● Go-ahead signal for cell to divide protein kinases
● Otherwise, enters G0 subphase ○ In response to DNA damage
○ Nondividing state in cells prior to G1
checkpoint
G2 checkpoint ○ Stimulate the transfer of
● Prevents the cell from entering several genes that may
mitosis when DNA is damaged inhibit cyclin-Cdk complex
● Opportunity for repair and ○ Prevents the cell cycle from
avoidance of proliferation of progressing
damaged cells ● Tumors can develop if both copies
● Helps maintain genomic stability of the tumor suppressor are
mediated
○ Mutant protein can no longer
carry out its function of
guarding the genome and
M checkpoint suppressing unregulated
● Prevents the cell from continuing growth
division if any chromosomes are not EX. T53
attached to spindle fibers
● Initiated during anaphase Mitogen
● When bound to mitogen receptors in
Growth factors the plasma membrane, the intracell
● Released by certain cells signalling pathway is activated
● Stimulate other cells to divide
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● Results in the formation of cyclin- ○ Activated by extracellular
Cdk complex signals that bind to the cells’
● Retinoblastoma proteins are then surface
phosphorylated, thereby ○ Results in a cascade of
inactivating them reactions in the cell that lead
○ Subsequent dissociation to apoptosis
from the transcription
regulators allows for the safe Initiator caspases
activation of cell proliferating ● Initiative process of apoptosis
genes ● Executioner caspase carries out
mass degradation of proteins that
Apoptosis lead to cell death
● Programmed cell death
● Occurs when cells have been ➔ The number of cells in a
exhausted or are no longer needed tissue/organ is highly regulated
● Mediated by an intracellular
proteolytic cascade Contact inhibition
EX. Human body ● Density-dependent inhibition
● Most dendrites undergo ● Normal cells stop proliferating when
apoptosis in a developing they form a monolayer in a culture
nervous system dish
● Most somatic cells undergo ● When a few cells are removed, cells
apoptosis during embryonic at the edge begin to divide until the
development to form fingers gap has been duly filled
and toes ● Cancer cells keep dividing and piling
● Constant apoptosis in bone on top of each other
marrow and liver cells ○ Do not exhibit contact
inhibition
○ Ignore cell cycle checkpoints
MECHANISMS FOR APOPTOSIS and controls
● Intrinsic pathway
○ Mitochondrial pathway is
activated by intracellular
signals of when cell is
stressed
○ Involves the release of
proteins from the
mitochondria
● Extrinsic pathway
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CANCER BIOLOGY Contact inhibition No contact inhibition
Controlled growth Uncontrolled growth
Cancer
Specialized cells Nonspecialized cells
● Malignant tumor or neoplasm (new
growth) Normal chromosomes Abnormal chromosomes
● Characterized by uncontrolled Undergo apoptosis No apoptosis
growth and spread of abnormal cells
● Encompasses a large group of HALLMARKS OF CANCER GROWTH
diseases ● Sustaining proliferative signaling
● Evading growth suppressors
CHARACTERISTICS OF CANCER CELLS ● Activating invasion and metastasis
● Hyperplasia ○ Active migration and spread
● Anaplasia to other tissues
● Dysplasia ● Enabling replicative immortality
● Large, variably shaped nuclei ○ Unlimited capacity to
● Small cytoplasm volume relative to replicate
nuclei ○ Unlike regular cells that have
● Variation in cell size and shape limits to their replicative
● Poorly defined tumor boundary capacities
● Inducing angiogenesis
Hyperplasia ● Resisting cell death
● Large number of dividing cells
● Continue replicating regardless of Angiogenesis
genome stability ● Blood vessel formation in growing
● Can ignore cell cycle controls tumors
● Meant to supply nutrients to the
Hypertrophy tumor growth
● Increase in size of cancer cells
EMERGING HALLMARKS
Anaplasia ● Avoiding immune destruction
● Loss of normal specialized cell ○ Avoiding interaction with the
features body’s immune system
● Deregulating cellular energetics
Dysplasia ○ Alternative metabolic
● Disorganized arrangement of cell pathways arise to generate
growth energy

NORMAL CELLS CANCER CELLS ENABLING CHARACTERISTICS

● Tumor-promoting inflammation
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● Genome instability and mutation CANCER PROGRESSION
● Mutation
STAGES OF CANCER DEVELOPMENT ● Hyperplasia
● Initiation ● Dysplasia
● Promotion ● In situ cancer
● Tumor Progression ● Invasive cancer

Initiation ➔ Tumors evolve by repeated rounds

● A single cell acquires a mutation of mutation, proliferation, and
● Mutated cell progeny becomes the natural selection
dominant clone in the tumor ➔ Some cancers have multiple
○ Proliferation of clones malignant clones with their own set
facilitate the increase in of mutations
population size ◆ Reflects tumor’s origin
○ Affects cells at risk of
acquiring additional Metastasis
mutations ● Occurs when the cancer has spread
to other tissues
Promotion ● Gives rise to a tumor colony in a
● Mutant cell ignores controls and new site (secondary tumor)
keeps accumulating mutations ● Cells of a primary tumor in
● Keeps on dividing and undergoing epithelium must cross the basal
epigenetic change lamina (basement membrane) then
● Leads to tumor formation migrate to connective tissues
● Then travel to blood and/or
lymphatic vessels
● Exit from bloodstream/lymph nodes
to proliferate in new location
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Benign ●Cancer has spread within the
- Non cancerous general region of its origin
- Either cannot spread or extremely 4. Metastasized
slow
- Generally do not return if removed Lymph nodes - small lumps of tissue which
- Can become premalignant then consists of masses of lymphocytes &
malignant macrophages (wbc)
- “-oma” suffix - Lymphocytes - b & t cells
Pre-malignant - Develop in bone
- Not yet cancerous marrow
- But has the potential to be - B mature in bone
malignant - T maure in thymus -
Malignant primary lymphoid
- Cancerous organ beneath
- Cells in a malignant tumor can grow breastbone sa may
& spread level ng heart
- Primary lymph nodes - fetal liver,
In situ cancer - abnormal cells are present bursa of fabricius (b cells) t - thymus
but not yet spread - Secondary lymphoid organs -
lymphatic system (lymphoid
STAGES system)
0. Carcinoma in situ - In vertebrates
1. Localized - Part of circ & immune
● Small tumor system
● The cells have passed - Functions : immune defense,
through the basal lamina maintenance of fluid levels, absorb
● Not yet grown deeply into of dig tract fats, removal of cell
the tissues waste
● Lymph nodes not affected
2. Early Locally advanced Cancer cells can turn on the angiogenic
● The tumor has grown switch - induce blood vessel formation in
● A lump is present in the tumor for supply of nutrients
lymph node
● Some lymph nodes are Tumorigenesis - development of fumor
affected
3. Late Locally advanced Carcinoma - from epithelial cell (breast,
● More lymph nodes are prelate, lung, pancas, colon)
affected
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Sarcoma - connective & supportive tissue, - Higher freq of dna rep, lower prob of
nerve - develops from cells originating in dna to acquire mut
sentinel(?) celsl outside bone marrow - Stochastic cancer
(bone, carti, fat)

Lymphoma, leukemia - hematopoietic

cells that leave marrow & mature in lymph
nodes, blood

Germ cell tumor - derived from newly

potent cells often present in testicle/ovary

Blastoma - immature precursor

cells/embryonic tissue

Proto-oncogenes, tumor suppressor genes

- Retinoblastoma, t53 ts genes
- Proto onco - myc
- Code for proteins involved in
signaling pathways that regulate
cell surv, growth, divi
- Some also code for prots involved in
dna repair, mediate damage
response, modify chromatin
- others code for proteins that reg cll
cycle for apoptosis
- When mutated they cant execute
their functions, leading to excessive
cell prolif

Correlate lifetime risk of cancer w/ # of divi

of self-renewing ells maintiang homeo
(stem cells)
- V high
- Coeff fo detrmination
- ⅔ (0.66)
- Amt of variability in y accounted for
in x
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STEM CELLS ● Proteins that turn on the expression
of genes that would convert
Stem cells specialized cells into stem cells
● Can replicate themselves or ● Normally expressed in embryos
differentiate into other cell types
● Primarily concerned with self- Progenitor cells
renewal and differentiation ● Precursor cells that are only partly
● Found in embryos and adult cells differentiated
● Found in fetal and adult tissues
STAGES OF STEM CELL DEVELOPMENT ● Divide and give rise to differentiated
● Totipotency cells
● Pluripotency
● Multipotency Hematopoietic stem cells
● Unipotency ● Myeloid progenitor cells
○ Neutrophils
Totipotency ○ Basophils
● Zygote stage ○ Eosinophils
● All types of cells can be formed ○ Monocytes
○ Germ cells and ○ Erythrocytes
extraembryonic structures ● Lymphoid progenitor cells
(placenta) ○ Natural killer cells
○ T-cells
Pluripotency ○ B-cells
● Blastocyst stage
○ Pre-implantation embryo
● All types of cells can be formed,
except extraembryonic structures

Multipotency
● Gastrula stage and adult stage
● Can form several types of tissue
cells

Unipotency
● Adult stage
● Can only form a single type of cell Vectors
● Can carry genes for reprogramming
Reprogramming factors factors
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● Can be delivered to a differentiated
cell in a culture dish via viral
transaction
● Cells that have integrated these
genes can be selected with specific
markers and screened for the
expression of desired proteins
EX. pLentG-KOSM

Induced pluripotent stem cells

● Can be derived from specialized
cells upon the insertion of
reprogramming prescription factor
genes
○ Oct4, Sox2, Klf4, Myc
● Requires the extraction of inner cell
mass from an embryo

Stem cell treatments

● The US-FDA has only approved
umbilical stem cell treatments
○ Hematopoietic stem cell
products
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ASEXUAL AND SEXUAL ● Release of specialized cells that can
REPRODUCTION grow into new individuals
EX. Sea sponges

MODES OF ORGANISMAL REPRODUCTION

Fragmentation
● Asexual
● Breaking of the parent organism into
○ Offspring from a single
several pieces
parent
● Some or all of the pieces develop
● Sexual
into complete adults
○ Offspring from a fusion of
EX. Sea stars
haploid gametes
○ While more complicated in
Parthenogenesis
preparation, confers the
● Unfertilized egg develops into
advantage of genetic
haploid adult
variation and evolution
EX. Bees, ants, wasps
○ Internal & External

Hermaphroditism
MODES OF ASEXUAL REPRODUCTION
● An individual organism is functional
● Fission
as both male and female mates with
● Budding
another member of the same
● Gemmules
species
● Fragmentation
● Some organisms of the species may
● Parthenogenesis
be asexual
● Hermaphroditism
EX. Earthworms
● Sequential hermaphroditism
○ Protogyny
Sequential hermaphroditism
○ Protandry
● An organism reverses their sex
during their lifetime
Fission
● Parent separates into 2 or more
Protogyny
approximately identical individuals
● An organism is born female then
EX. Cells
reverses to male
EX. Saddle wrasse (fish)
Budding
● The larger mate becomes
● New offspring split off from the
male, the smaller male
parent
becomes female
EX. Hydra
● When a terminal face male
dies, the largest female of
Gemmules
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the social group becomes ● Urethra, 3 cylinders of erectile
male tissue
● Head - glans - covered by
Protandry prepuce/foreskin
● An organism is born male then
reverses to female Spermatogenesis
EX. Gilthead seabream (fish) ● Gametogenesis in males (gamete
prod)
MALE REPRODUCTIVE SYSTEM ● Stem cells that give rise t sperm are
at the outer edge fo the
Testes seminifurous tubule
● Produce sperm in highly coiled ● When they div, prod spermatogonia,
seminiferous tubules which div into spermatocytes
● Sperm travel through the epididymis
for approximately 3 weeks Ext - clit, 2 labia sets (minora, majora)
○ During which they become Int - ovaries, systems of ducts & chanbers
mature and motile
ovaries - prod eggs & rep hormones
External organs = penis & scrotum Oviduct - fall tube, extends from uterus to
Internal organs = gonads, accessory funnel like opening at each ovary
glands, ducts
Upon ovul, egg is propelled into ovi, then
Ejacultory duct into uterus
● Sperm is propelled through the vas
deferens, which is joined to the Inner lining - endometrium
seminal vesicle cervix - neck of uterus, opens into the
● Opens into the urethra vagina

Accessory glands Oogenesis - gam production

● Produce secretions that combine - Begins in female mebryo w prod of
with sperm to make semen oogonia
○ Seminal vesicle (2) - Undergoes cell div, process is
○ Prostate arrested at peop 1 of meiosis before
○ Bulbourethral gland birth
■ Clear mucus that - Each prm oocyte is enclosed ina
neutralizes the acidic folicle
urine in the urethra - From puberty, hormones periodcally
sitmuate a cmall grop of follicles to
Penis stim development
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- 1 follicle fully matures each month, - After 4 days, blastocyst is produced
with prim oocyte completing - Embryo implants into endo
meiosis 1 then proceeding to - Gestation - 38 weeks fom fert to
meiosis 2 (halted at met stage) expulsion
- Secondary oocyte arrested at met 2
is released during ovul Spermatogonium - Primary spermatocyte
- When a sperm fertilizes it, mei2 (46), then secondary (23) undergo meiosis
resumes 2, producing 2 spermatid each (also 23)
- fert takes place in oviduct
- 2nd ooyte in fall tube meets, In oocyte, 1 is blogger than the rest bc
aprosome fo the sperm rleases unequal division of cyto - egg cell shea
enzymes allowing it to penetrate (ovum) - all the polar bodies degenerate
jelly coat of egg
- Sperm plasma membrane fuses w The xygote ndergoes cell divison to give
egg pm rise to tissues & organ systems - thru cell
- Sperm head disconnecst from division , makes way for growth &
glgellum devlpmnty
- once finds its way past zona
pellucida, cortical rea occurs
- Cortical granule sinside 2nd oocyte
fuse w pm of cell, causing enzymes
inside granules to be released to the
zp
- Results in formation of fertilization
membrane - hard matrix
inpermeable to other sperm cells
- Prevents polyspermy - fert of egg by
more than 1 sperm
- Another mech is the fast blanket -
opening of sodium ion channels in
egg pm whenit comes into conatc w
pm of sperm
- Sodium flows into egg cell, resulting
in chane in membrane potential
- Prevents addtl sperm from fusing to
the egg pm

24 hrs after fert - zygote undergoes series

of cell div