Cell Final (New Material)

Front 1

What are the 4 phases of the cell cycle and what happens in each?

Back 1

1) G1 phase - Primary growth

2) S phase - DNA synthesis

3) G2 Phase - secondary growth

4) M phase - mitosis (nuclear division) and cytokensis (cytoplasmic division)

Front 2

Interphase

Back 2

Is made of G1-S-G2

Front 3

Cell cycle times (Embroys, yeasts, cultured human cells, human liver cells, neurons)

Back 3

Cells have different cell-cycle times

a) Embryos: 30/cycle

b) Yeasts: 2 hours/cycle

c) Human cells: 20 hours/cycle

d) Human liver cells: 1year/cycle

e) Neurons: No more divisions

Front 4

G0 Phase

Back 4

This withdraws a cell from the cell cycle. These are non-dividing cells.

This is a resting state (Quiescense).

Neurons and skeletal muscle are in this state

Front 5

Oncogene

Back 5

This can induce a "quiescense" or "resting" cell to re-enter the cell cycle.

Front 6

Essential Processes of Cell Cycle (Enter S, Enter M, Exit M)

Back 6

These are the essential processes that occurs at the three points

a) Enter S phase: This triggers the DNA to replicate.

b) Enter M phase: This triggers the mitosis to start, and the mitotic spindle to assemble

c) Exit M phase: This triggers the completion of mitosis, and it proceeds to cytokinesis. Cell division is complete.

Front 7

Two different types of Cdk

Back 7

There is S phase Cdk and mitotic Cdk.

Front 8

S phase Cdk Activation

Back 8

S-phase Cdk remains inactive in G1 phase.

Then S-cyclin binds and phophorylates S-Cdkk, it becomes activated, and triggers "DNA replication"

S-phase Cdk binding to S-cyclin enters the cell into the S-phase

S-phase Cdk inactives with the degradation of S-cyclin in S phase

Front 9

Mitotic Cdk Activation (General View)

Back 9

Mitotic cdk remains inactive in G2 phase.

Then M-cyclin binds to Mitotic Cdk, phosphorylating it -- thus activating Mitotic Cdk.

This activation triggers Mitosis, entering the cell into M-phase. Then the M--cyclin is degraded in M-phase.

Phosphorylation of M-Cdk by M-cyclin triggers the cell to enter Mitosis

Front 10

Three functions of Cyclins

Back 10

a) they are expressed in cyclic fashion (in waves) because their concentration varies throughout cell cycle, driving the activation of cyclin-Cdk complexes. The rapid fall is when they are degraded

b) no enzyme activity

c) they activate Cdks by binding to them. They also direct Cdks to target proteins

Front 11

characteristics of Cdks

Back 11

They are protein kinases in the "Cell Cycle Control System".

Cdk (Cyclin dependent kinases)

a) they are activated by cyclins

b) They contribute to their own inactivation

Front 12

Positive feedback of M-Cdk

Back 12

Fill in information

Front 13

Kinases and Cdk activation

Back 13

Even with the cyclic concentrations of Cyclin, Cyclin-Cdk gets activated at appropriate times abruptly.

This trigger of activation is done so by specific protein kinases.

For cyclic-Cdk to be activated, Cdk has be phosphorylated at one site and dephosphorlyated at other sites by "Protein Phosphatase".

Front 14

Degradation of Cyclin

Back 14

Activation of M-Cdk by M-cyclin also activates APC

APC (Anaphase promoting complex)

Front 15

Cell cycle control system

Back 15

The cell has checkpoints and feedback process that help to make sure DNA replication, Mitosis and so on go according to plan.

Front 16

Three checkpoints

Back 16

These are molecular brakes incorporated into the cell cycle.

a) G1 check point

b) G2 check point

c) During Mitosis

Front 17

First Checkpoint

Back 17

a) G1: allows cell to confirm whether the environment is favorable for DNA replication -- before entering into S phase.

Extracellular signal, sufficient nutrients are needed, otherwise cell will delay, and can even enter into G0 phase.

Front 18

Second Checkpoint

Back 18

b) G2: allows the cell to make sure that the DNA has been replicated completed, and that any damaged DNA has been repaired -- before entering into M phase

Front 19

Third Checkpoint

Back 19

c) During mitosis: This makes sure that the replicated chromosomes are properly attached to the cytoskeleton machine (mitotic spindle) -- before the chromosomes are pulled apart by the spindles.

Front 20

Turning a protein "On" and "Off"

Back 20

Phosphorylation and dephosphorylation are used to turn the protein on or off -- used by the "Cell Cycle Control System".

Front 21

Why are activity of Cdks "cyclic" manner?

Back 21

These kinase proteins called "Cdks" are activated at very specific times by cyclin. and then they become quickly inactivated by degration. So since the activity of the kinases rise and fall, the cyclic matter is observed.

Front 22

What are kinases?

Back 22

A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation).

Phosphorylation usually results in a functional change of the target protein (substrate) by changing enzyme activity, cellular location, or association with other proteins.

Kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction.

Front 23

4 major cyclins and Cdks

Back 23

1) Cyclin A: forms "S-Cdk" complex. Pairs with Cdk2 [G1 checkpoint]

2) Cyclin B: forms "M-Cdk" complex. Pairs with Cdk1 [G2 Checkpoint]

3) Cyclin D: forms "G1-Cdk" complex. Pairs with Cdk4, Cdk6

4) Cyclin E: forms "G1/S-Cdk" complex. Pairs with Cdk2

These cyclic-cdk formation depends on extracellular signals, and when activated, stimulates cell growth.

Front 24

Degradation of Cyclin

Back 24

This is what cases the spark fall in cyclin graphs.

Specific enzymes add "ubiquitin chains" to the appropriate cyclin. This is then directed to "Prteasome" for destruction.

Inactivation of M-Cdk, by the degration of M-cyclin, pulls the cell out of Mphase.

Front 25

Cdk Inhibitor protein

Back 25

These are the molecular brakes used by the "Cell cycle control system".

This blocks activity of one or more cyclin-Cdk complexes.

Front 26

Mitogens

Back 26

Extracellular signals that cause cells to multiply.

Front 27

Origins of replication

Back 27

These are nucleotides sequences that are scattered along each chromosome.

These sites control the initiation and completion of DNA replication by recruiting specific proteins.

Front 28

Origin of Recognition Complex (ORC)

Back 28

This complex remains bound to the Origin of replication sequence throughout the cell cycle.

It helps regulatory protein to have a place to land before the start of S phase.

Front 29

Pre-replicative complex

Back 29

A regulatory protein called "Cdc6" increases in G1 phase and attaches to the ORC during G1.

This basically gets the entire process ready to go into S-phase.

Front 30

Entering S phase

Back 30

Once the "pre-replicative complex" has been formed, and the S-Cdk has been activated, the whole thing can start -- and enter S phase.

Front 31

Preventing Re-replication

Back 31

To prevent the "re-replication" of the DNA, activated S-Cdk phosphorylates Cdc6 and disassembles the "Pre-replicative complex",

Phosphorylation of Cdc6 also marks the protein for degradation.

Front 32

Cohesins

Back 32

They are the protein complexes that form protein rings that hold sister chromatids together after replication.

They are broken apart during the late mitosis period, so they can be pulled apart by mitotic spindles.

Front 33

Two types of cell death

Back 33

a) Necrosis: cell death due to the unfavorable environemental change. Osmotic imbalance, for example.

b) Apoptosis: programmed cell death. lysomosmes vessicles start to degrade organelles

Front 34

Activation of M-Cdk (Mphase)

Back 34

Activation of this protein complex triggers the replicated chromosomes to condense and form rod like shapes.

Mitotic spindle also starts to assemble.

Activates Condensins by phosphorylation. This helps chromosomes condense

Activation of one M-Cdk in turn activates others M-Cdks.

Front 35

Centrosomes in M phase

Back 35

In M phase, centrosomes duplicate [Interphase]

They are the microtubule-organizing center.

Each centrosome contains a pair of centrioles, made of mircotubules (cylindral)

Front 36

Condensins

Back 36

Protein complexes that help chromosomes condense.

Front 37

Condensins and Cohesins

Back 37

They work together to keep sister chromatids together.

Front 38

Four stages of Mitosis

Back 38

1) Prophase

2) Metaphase

3) Anaphase

4) Telophase

Front 39

Prophase

Back 39

1) Replicated chromosomes (in S-phase) condense

2) Assembly of mitotic spindle outside nucleus.

3) Nuclear envolope breaks down due to "phosphorylation of Lamins"

4) Microtubles attach to centrosomes at "Kinetochore" site.

Front 40

Metaphase

Back 40

1) The mitotic spindle gathers all chromosomes to the equator, between the two spindles.

2) Duplicated chromosomes line up individually on the spindle (unlike in meiosis where the chromosomes are lined up with their homologous pairs)

Each sister chromatid has 2 microtubles attached at the kenetochore from either sides.

Front 41

Anaphase

Back 41

1) Sister chromatids are split apart

2) Microtubles attached at kinetochore get shorter

3) Spindle poles move apart

4) Cohesion rings are boren

Front 42

Telophase

Back 42

1)The chorosomes arrive at the poles

2) Nuclear envelope starts to reassemble by de-phosphorylation of "Lamins"

3) Formation of 2 nuclei

4) Contracticle ring assembled

Front 43

Cytokinesis

Back 43

This starts in anaphase and continues through telophase.

Cytoskeleton structure "Contractile ring" assembled in Telophase is responsible for cytoplasmic division.

It consists of actin and myson filaments

Front 44

Apoptosis (family)

Back 44

It is programed cell death.

Caspace family of "proteases", members of which are made as inactive precursors called "procaspases"

These procaspases are activated when they become cleaved "proteolytic cleavage"

Front 45

Procaspases

Back 45

Procaspases become activated when their ends are cleaved.

For their ends to be cleaved, member of the Bc12 family need to become involved.

Bc12 (Bax and Bak) in mitocondria channels induces "cytochrome c" to be realized from the mitochondria.

Cytochrome C attaches to "adaptor proteins" -- which then "activate procapase"

Front 46

ThreeFourextracellular signals

Back 46

a) survivor factors: promotes cell survival by suppressing apoptosis

b) mitogens: it stimulates cell division by removing Rb protein

c) growth factors: stimulate cell growth

d) myostatin: this normally inhibits growth and proliferation of moblasts.

Front 47

3 useful factors of Cell Death

Back 47

a) Digit formation in mice

b) metamorphosis of tadpoles

c) precise number of neurons connected to target cells.

Front 48

Sister chromatids

Back 48

Duplicated chromosomes

Front 49

Centrosome

Back 49

-- Microtubule-organizing center.

-- y-tubulin rings

-- inside the centrosome, there are a pair of centrioles

-- Centrioles are composed of microtubules

-- During Prophase, the centrioles start growing the mircrotubles and they come out of the y-tublin rings in the centrosomes.

Front 50

Mitotic spindle

Back 50

Complex cytoskeleton machine. Composed of microtubules to separate replicated chromosomes.

Front 51

Three kinds of microtubules in mitotic spindle

Back 51

a) aster:

b) kinetochore

c) interpolar

Front 52

Mitotic Spindle Equator

Back 52

Where the chromosomes are aligned during Metaphase

Front 53

Cytokenesis cytoskeleton structure (animal and plants)

Back 53

a) Animals: A contractile ring forms made of "Actin" and "mysoin" filaments.

b) Plants: Phragmoplast specialized structure is involved, made of microtubles.

Front 54

Diploid (body cells)

Back 54

These cells have 2 sets of chromosomes, one set maternal, the other paternal. These chromosomes are similar, except for sex chromosomes.

Front 55

Sex chromosomes

Back 55

Specialized chromosomes present in some organisms that separate males from females.

Front 56

Alleles

Back 56

Genes that are in varient versions.

When sexual reproduction occurs, the new individuals are then present with new combination of alleles.

Front 57

Haploid cells

Back 57

These are called germ cells or Gamtes

Unlike Diploid which contains 2 sets of chromosomes, one from maternal, other from paternal. Haploid only contains 1 set of chromosomes (half of that set is maternal, half is paternal)

Central process in sexual reproduction.

Ex. Egg and sperm are gamates

These are produced when a diploid cell goes through miosis.

Front 58

Zygote

Back 58

When two haploid cells fuse to form a diploid.

Ex. sperm and egg fuse to form a fertilized egg (this fertilized egg is a zygote)

Front 59

Homologous chromosomes

Back 59

Also called "homologues or homologs"

They are parental chromosomes which are similar, but not identical. One is from maternal, other from paternal.

Front 60

Sister chromatids

Back 60

Twin copies of each replicated chromosome. They are held together by cohesins. They are identical chromosomes.

Duplicated during S-Phase in a cell

Front 61

Chromatid

Back 61

Just 1 half of a sister chromatid (one chromtid). It is joined to the other chromatid at the "Centromere"

Front 62

Daughter chromosomes

Back 62

These are separated sister chromatids

Front 63

Where does Miosis being?

Back 63

Miosis begins in specialized diploid germ line cells in the tests (guys) or ovaries (girls).

Front 64

Meisos 1 (4 phases)

Back 64

a) Prophase I

b) Metaphase I

c) Anaphase I

d) TelophaseI

Front 65

Prophase I

Back 65

(Replication of DNA has already happened)
a) Condensation of chromosomes, sister chromatids, identical chromatids.

b) Snyapsis/pairings of homologous chromosomes

c) Crossing over occurs between homologous chromosomes

d) Nuclear envolopen and nucleoli dissolves

Front 66

MetaphaseI

Back 66

[Terminal chiasmata holds homologous pairs together]

a) The microtubles form spindles, attaching to 1 side of each centromere (so either sides of homologous chromosomes)

B) The homologous chromosomes (with 2 sister chromatids) line up at equatotial plane

Front 67

Anaphase I

Back 67

a) The spindle fibers shorten

b) The homologous chromosomes are split and migrate to opposite poles [Random orientation results in "Independent Assortment"]

[The sister chromatids are still together. Just the homologous chromosomes are separated]

Front 68

Telophase I

Back 68

a) The homologous chromosomes are separated, and sister chromatids on either sides of the poles.

b) These sister chromatids are no longer identical because of crossing over.

c) Both poles have haploid number of chromosomes.

d) Cytokinesis, nuclear envelope and nuclei forms

Front 69

Result of Meiosis I

Back 69

Two daughter cells with haploid chromosome number are formed.

Front 70

Prophase II

Back 70

a) Degradation of nuclei and nuclear envople

b) Spindle fibers start growing.

Front 71

Metaphase II

Back 71

a) The spindle fibers attach to both sides of the centromere (Either sides of sister chromatid)

b) Chromosomes align at equator

Front 72

Anaphase II

Back 72

a) Spindle fibers contract

b) The sister chromatids are seperated by spindle fibers

Front 73

Telophase II

Back 73

a) Both poles have single stranded chromosomes.

b) Cytokensis occurs, nuclear envople and nuclei forms

Front 74

Result of Meiosis II

Back 74

There are 4 daughter cells (from 2 daughter cells after miosis I)

The daughter cells now contain half the chromosomes (Haploid)

Front 75

3 Features unquie to Miosis

Back 75

a) Synapsis: homologous chromosomes pair up with sister chromatids (2 pairs of sister chromatids)

b) Homologous recombination: Due to synapsis, there is crossing over of homologous chromosomes

c) Reduction division: Two successive divisions.

Front 76

Chiasma

Back 76

Structure formed when homologous chromosomes cross over. (Looks like an X, where they exchange genetic material)

Front 77

Genetic variation in gametes

Back 77

a) Independent assortment of maternal and paternal homologs in miosis I

b) crossover in prophase I

Front 78

Non-disjunction

Back 78

When the homologs fail to separate properly.

Either extra chromosomes, or one less chromosomes

-- Down syndrome: caused by extra chromosome, chromosome 21.

-- aneuploidy: when the eggs give rise to the wrong number of chromosomes. more often seen in eggs.

Front 79

Molecular events of "Crossing over" (Recombination)

Back 79

a) Double strand break: by a specialized enzyme,

b) Limited degration from 5' ends

c) Pairings of paternal/maternal strands

d) Cross strand exchange -- Holiday junction formed

e) resolved by strand cutting

Front 80

Holiday Junction

Back 80

It's a mobile junction between four strands of DNA

Front 81

Tissues

Back 81

Made of cells with internal framework of cytoskeleton filaments, but also "Extracellular matrix" which cells secrete around themselves.

Front 82

What are the 4 major types of animal tissues?

Back 82

a) Connective

b) Epithelial

c) Nervous

d) Muscular

Front 83

5 types of epithelial cells

Back 83

a) simple

b) stratified

c) columnar

d) cuboidal

e) squamous

Front 84

Epithelial cell sheets

Back 84

They form into organs during embroynic development

Front 85

Adhesion belt

Back 85

It provides adhesion and movement in organs

Front 86

2 faces of Epithelial cells

Back 86

a) apical surface: free and exposed to the air, or to a watery fluid

b) basal surface: rests on other tissue, connective, to which it is attached.

Front 87

Basal lamina

Back 87

It supports the basal surface of the epithelium. Made of thin, tough sheets of extracelluar matrix.

Front 88

Five types of cell junctions

Back 88

a) Tight junction

b) Adhesion junction

c) Desmosome

d) Gap junction

e) Hemidesmosome

Front 89

Tight junction

Back 89

-- It seals neighboring cells together so water soluble molecules cannot leak between them.

-- Connects plasma membrane of adjacent cells (like epithelial)

-- Barrier to protect organs

Front 90

Adhesion Junction

Back 90

-- Connect s actins of adjacent cells

Connecting protein (Cadherins)

Front 91

Cadherins

Back 91

Important connecting proteins.



For Example, it can bind directly from the plasma membrane of one cell to the plasma membrane of another cell.

Front 92

Desmosome

Back 92

Another type of cell junction.

-- It connects intermediate filaments

(Binds epithelial cells to another epithelial cell)

-- Different type of cadherin molecule anchored inside the cell that connect to intermediate "keratin" filaments.

Front 93

Gap junction

Back 93

Another type of cell junction

-- They are protein channels made of "Connexins"

-- Connexins form channels across 2 plasma membrane

Front 94

Hemidesmosome

Back 94

-- It anchors cells to ECM through integrin

(Binds epithelial cells to basal lamina)

-- Uses "Intergrin" molecules (like desmosome and adherens junction uses "Cadherins")

Front 95

ECM (3 properties)

Back 95

a) Collagen: it is one of the major components of ExtraCellularMatrix

b) Laminin: Trimers form a cross structure

c) It also contains fibronectin, gelatin

Front 96

Skin blisters

Back 96

Mutations in ECM genes can cause them

Front 97

Tumor

Back 97

It is formed when there is an abnormal growth in cells (neoplasm) forming a "Solid Lesion".

-- Caused by multiple mutations in somatic cells

Front 98

Neoplasm

Back 98

It is abnormal growth in cells

Front 99

6 characteristics of cancer cells

Back 99

1) Reduced dependence on signals from other cells, outside. Ex. mutation in Ras gene

2) Less prone to go through apoptosis. Usually because p53 gene is mutated

3) Proliferate indefinitely

4) Genetically unstable, increase in mutation

5) Abnormally invasion (lack adhesion molecules such as cadherins to hold the cells in place)

6) They can survive and proliferate in foreign cells, when normal cells would die if they are misplaced.

Front 100

Classification of cancer genes

Back 100

a) Oncogene : gain of function, excessive proliferation

b) Tumor-suppressor gene: loss of function, excessive proliferation.

Front 101

Difference between Proto-oncogene and Oncogene

Back 101

-- Proto oncogene: they are normal gene that serve many functions in a cell such as apoptosis.

-- Oncogene: Is what happens to the "proto-oncogene" after mutation. So a Proto-oncogene becomes oncogene

Front 102

Three ways "Proto-oncogene" becomes "Oncogene"

Back 102

a) Mutation: There was a mutation in coding sequence. This results in a hyperactive protein (made in normal amounts)

2) Gene amplification: A normal protein (not hyperactive), but it is produced excessively.

3) Chromosome rearragement: Either causes a protein to become hyperactive (fusion to actively transcribed gene) or causes normal protein to be produced excessively. Due to elevated transcription

Front 103

Mutations in "oncogene" and "tumor suppressor gene"

Back 103

a) Oncogene: NORMAL (promotes growth) MUTATION (hyperactivity, overproduction)
-- Gain of function

b) Tumor Suppressor Gene: NORMAL (growth check, checkpoint) MUTATION (no checkpoint induces cancer)
-- Loss of function

Front 104

4 mutations needed for Cancer Formation

Back 104

They are called "mutiple-hit" model

In colon cancer
1) Mutation in APC (tumor suppressor gene) leads to "Neoplasm"

2) Mutation of ras gene (oncogene) leads to "small tumor"

3) Mutation in another tumor suppressor gene, leads to "large tumor"

4) Mutation in p53 (tumor suppressor gene) [involved in apoptosis], leads to metastatic cancer

Front 105

Tumor sizes and characterists

Back 105

a) 10 8 : Visible on x-rays

b) 10 9: Palpable

c) 10 12: Causes death

Front 106

Breast cancer

Back 106

Takes 100 days for breast tumor to double

Front 107

When there is NO Wnt Signal

Back 107

This is Normal..

When there is No Wnt signal, the Receptor remains in active

Because the receptor is inactive, the Signaling protein remains inactive

Because signaling protein is INACTIVE, APC is active

APC is a tumor suppressor gene, and when active, it degrades "B-Catenin"

Because B-Catenin cannot bind to TCF complex, TCF remains inactive

As a result, Wnt-Reponsive Genes Stay OFF

Front 108

When there IS a Wnt Signal

Back 108

Wnt Signal is received by "Receptor"

Receptor becomes Activated

Activated Receptor activates "Signaling Protein"

Activated "Signaling Protein" turns APC off.

Because APC (tumor supressor gene) is now inactive, the B-Catenin cannot be broken down

Stable B-Catenin activates TCF complex

TCF complex begins transcription, proliferation of gut steam cells.

Front 109

Intracelluar key player proteins (Wnt)

Back 109

1) APC (tumor suppressor gene)

2) B-catenin (is degraded without Wnt signal, and when signal is present, it activates TCF complex)

Front 110

Leukemia and Anti-cancer drug

Back 110

Gleevec

Leukemia is caused by overproduction of white blood cells

-- Associated with oncogenic form of "Abl" protein kinase

-- Mutated, oncogenic Abl Protein Kinase would bind to a substrate, phosphorlyate, and this would induce a cell signal for proliferation and survival -- leading to leukemia

-- Gleevec would go bind to the ATP (phosphorlytaing) site of the Abl protein kinase. Now the subtract cannot be activated, thus no signal, no leukemia.