Unit 3 - Epigenetics, Mitosis & Cell Cycle Control

Question 1

Epigenetics

Answer 1

any process that alters gene activity without changing the DNA sequence

2 kinds:
1) Methylation (adding CH3 to DNA)
- hypermethylation can silence genes

2) DNA packaging
- DNA can be mostly packed but can become more tightly packed

**How genes are switched on or off by epigenetics distinguishes genes from others (eye cells vs. skin cells)
- genes are different based on how they are switched on or off

Question 2

Epigenetic Changes Are…

Answer 2

1) reversible
- methyl groups can be removed
- can switch from euchromatin to heterochromatin

2) heritable
- modifications can be passed onto future generations

Question 3

Heterochromatin and Euchromatin

Answer 3

Heterochromatin:
- tightly packed DNA
- doesn’t have a lot of genes
- transcriptionally silent

Euchromatin:
- Loosely packed DNA
- has lots of genes
- easier to be transcribed

**DNA can go back and forth between euchromatin and heterochromatin

a single gene:
- it would be expressed when in euchromatin – would be able to be transcribed

Question 4

X-Inactivation

Answer 4

one of the copies of the X-chromosome is inactivated

• the chromosome becomes very condensed so the genes become inactive (can’t be expressed)
• they become a barr body
• whichever X chromosome was inactivated in the parent cell will be inactivated in the daughter cells

**half of the cells will be inactive
- the maternal cells and the other half will inactivate the paternal cells

Question 5

Barr Body

Answer 5

when an X chromosome becomes inactivated

Question 6

In-class video: Background

Answer 6

they first estimated that the genome was made up of 30,000 genes, but then the number kept increasing
- humans have the same number of genes as mice and fish

Question 7

Angelman Syndrome

Answer 7

• the children have a jerky movement when they walk, have no speech

chromosome 15:
- if it was deleted from the father = other syndrome
- if it was deleted from the mother = angelman syndrome
*the genes knew were they were coming from

Question 8

Chromosome 15 Research

Answer 8

• Must be a tag or an imprint on the chromosome during egg and sperm formation in the previous generation
• Although the DNA sequence is the same, different sets of genes were being silenced depending on if they came from mom or dad

Question 9

Agouti Gene

Answer 9

ex: the yellow mice that eat so much they get diabetes

• A chemical tag called a methyl molecule (made of carbon and hydrogen) shuts down the agouti gene
• The fat yellow mothers gave birth to thin brown mice that didn’t have the gene
• he tags control gene expression through the epigenome

Question 10

Video: Epigenome

Answer 10

our genome is really hard to change but the environment around us changes all of the time
- the epigenome is built to respond to changes around us
- our experiences change the epigenome

ex: one group of mice = born to moms who nurtured them
second group = born to moms who didn’t nurture them

• the mice born to mean moms would bite
• what the mom brings affects the offspring
• less nurtured rats have epigenetic marks silencing the gene – causes them to be more stressed
• more nurtured rats could handle stress better bc they didn’t have anything silencing the gene

**epigenome varies from tissue to tissue

Question 11

Stem Cell Research

Answer 11

Identitical Twin EX: one has cancer and the other doesn’t
- epigenetic damage can cause cancer
- every time a stem cell has to repair injury, it injures us more
- We have genes that help to prevent tumors that epigenetically get silenced and we have genes that lose their methylation tags which causes tumors to grow

• Sandra took a drug that silenced methyl tag genes
• The meds reactivate genes

Question 12

Twins with Autism EX:

Answer 12

Doctors found that the hippocampus was smaller in the twin with autism

The hypothesis: the twins have the same genome but one of them has an epigenetic difference that leads to the different sizes in their brain structures (not in the other twin without autism)

• The environment molds our epigenomes

Question 13

Our Ancestor’s Health Can Still Impact Us

Answer 13

Environmental info was being imprinted on the egg and sperm at the time of formation

• The memory of famine can affect two generations later

*Our grandparents’ experiences affect our health

diff ex:
*If someone was exposed to an environmental toxin, they could get a disease – but now, the environmental toxin affects two-three generations later

Question 14

Mitosis

Answer 14

leads to the production of all other cell types (non-gametes cells)
- these are somatic cells

• divide the contents of the nucleus

Question 15

Somatic Cells

Answer 15

all body cells except for gametes and the cells that give rise to gametes

Question 16

Binary Fission

Answer 16

1) copy DNA
2) it then separates DNA equally into 2 daughter cells

*asexual reproduction
- how bacteria divides

Question 17

Cytokinesis

Answer 17

division of cytosol/other organelles in the cell being divided

Question 18

Beginning and End of Mitosis

Answer 18

Beginning:
- start with parent cell
- 2n cell

End:
- 2 daughter cells that are clones of the parent cell
- the daughter cells are idenititical to each other and the parent cell
– their DNA is exactly the same
- two 2n cells

Question 19

Functions of Mitosis

Answer 19

1) Growth
- anytime an organism wants to add cells it goes through mitosis
ex: zygote, 2-celled embryo, 8-celled embryo…

2) Repair/Replacement
- if you have damaged cells, these cells get repaired via mitosis
- bone marrow cells can divide quickly into diff kinds of cells like red blood cells

3) Asexual Reproduction
- the ability to reproduce without sperm and egg
ex: yeast

Question 20

Chromosome

Answer 20

structure carrying genetic material
- chromosome containing genes and non-coding DNA

• they are made up of nucleosomes, looped domains
• each chromosome has two sister chromatids

Question 21

Human Karyotype

Answer 21

humans have 46 chromosomes and 23 pairs
2n= 46
n= 23

human gametes: haploid
n = 23
- haploid with a total of 23 chromosomes

**you have one chromosome from mom and one from dad (maternal and paternal chromosomes)

**karyotypes are taken during prophase or metaphase

Question 22

Sister Chromatids

Answer 22

replicated chromosomes

Question 23

Kinetochore

Answer 23

protein structure where microtubules attach during mitosis

Question 24

Centromere

Answer 24

region where the sister chromatids attach to each other

Question 25

Cohesins

Answer 25

They act as glue that holds the sister chromatids together down their whole length

Question 26

Interphase

Answer 26

G1 + S + G2 = Interphase

Question 27

Mitosis: G0

Answer 27

resting stage - transcribing and translating (not currently dividing) - receives signal to divide **after the signal, cell now goes thru the cell cycle ----- - in humans, you start with the parent cell which is diploid (2n= 4)

Question 28

Mitosis: G1

Answer 28

- cell growth, transcription, translation - duplication of organelles - prepare for DNA Replication

Question 29

Mitosis: Synthesis

Answer 29

DNA Replication (s) stands for synthesis

Question 30

Mitosis: G2

Answer 30

- More growth, transcription, translation - prepares cell to divide - centrosomes appear

Question 31

Mitosis: Metaphase

Answer 31

chromosomes line up on the metaphase plate - the # of chromosomes in metaphase = same # in prophase 4 chromosomes - each composed of 2 sister chromatids - total of 8 sister chromatids in the cell - the metaphase plate is halfway in between the centrosomes

Question 32

Endromembrane System

Answer 32

- breaks into vesicle structures - reforms into daughter cells

Question 33

Microtubule Types

Answer 33

1) Kinetichore microtubules -- attach to the kinetichores of each chromosome - one microtubule attaches to each kinetichore 2) non-kinetichore microtubules - do not attach to the kineticore

Question 34

Mitosis: Anaphase

Answer 34

separating DNA - cohesins (proteins) will degrade - sister chromatids separate - kinetichore microtubules shorten - non-kinetichore microtubules lengthen so the cell elongates - motor proteins push against each other which causes the cell to get longer ---- **0 sister chromatids (bc we separated them)

Question 35

Mitochondria

Answer 35

- split between 2 daughter cells - divide by binary fission to reproduce in new cell

Question 36

Mitosis: Prophase

Answer 36

chromosomes condense - DNA becomes as tightly packed as possible - nuclear envelope degrades (breaks into little pieces) - centrosomes move to opposite sides of the cell - mitotic spindle forms --- centrosomes and microtubules that grow from it - 4 chromosomes, each w/ 2 sister chromatids

Question 37

Bacterial Chromosome

Answer 37

- in nucleoid region - gets a signal to divide - contractile ring which will get tighter until the cell splits into 2 result: - you get 2 daughter cells

Question 38

Cancer and checkpoints

Answer 38

cancer = problem with cell cycle control checkpoints = regulatory molecules at each checkpoint "decide" if division should proceed

Question 39

Mitosis: G1 Checkpoint

Answer 39

- if the checkpoint is good, the gate goes down and the process continues - is growth factor present? - is cell big enough? - is DNA undamaged?

Question 40

Mitosis: Telophase/Cytokinesis

Answer 40

- chromosomes decondense - nuclear envelope reforms - centrosomes and spindle disappear - cleavage furrow (the pt. where the cell is going to divide) forms - microfilaments (actin subunits) shorten result: - two daughter cells - each daughter cell is 2n = 4

Question 41

Mitosis: G2 Checkpoint

Answer 41

is DNA Replication complete?

Question 42

Mitosis: M Checkpoint

Answer 42

end up with 2 daughter cells - are chromosomes attached to kinetochores microtubules?

Question 43

What happens for Normal Cells if there's a problem:

Answer 43

- the problem gets fixed or it goes into apoptosis - in unregulated cell division, the problem doesn't get fixed and the checkpoint gets ignored - normal cells don't divide unless there's a growth factor present properties of normal cells: - growth factor, anchorage dependence, and contact inhibition

Question 44

Apoptosis

Answer 44

Apoptosis = cell suicide - highly regulated cell - cell DNA degrades - cell blebs apart and dies - remnants get engulfed by other cells

Question 45

Growth Factor

Answer 45

stimulates cells to divide - this ensures that the cells start and stop reproducing at the right time - each growth factor has a diff. receptor

Question 46

Signal Transduction Pathway

Answer 46

external signal --> internal response 1) reception: - signal binds to a receptor - then the receptor gets activated - when it gets activated, there's a shape change 2) Transduction - once something gets activated, it activates the next thing - relay molecules in signal transduction pathway 3) Response - activation of cellular response - tells the cell to divide - the signal can't come into the control system bc there's multiple pathways

Question 47

Anchorage Dependence

Answer 47

cells must be attached to divide - cells adhere to other cells, extracellular matrix, or tissue culture **they have to be attached to the right thing to be able to divide

Question 48

Contact Inhibition

Answer 48

crowded cells stop dividing - each tissue type have different degree of crowdedness before they stop dividing ex: imagine ptree dish with cells in it that keep dividing **contact inhibition = density-dependent inhibition - it's the same thing

Question 49

Properties of Cancer Cells

Answer 49

1) a tumor grows from a single cancer cell - benign tumor (not cancerous) - localized to one area - they can be removed (not as hard to treat) - cells divide with no growth factor present - cells ignore contact inhibition (keep growing past the limit) 2) cancer cells invade neighboring tissue - malignant tumor (cancerous) - not localized or encapsulated - cells spread out into different tissues - harder to treat 3) Cancer Cells spread to other parts of the body - Metastasis - cells ignore anchorage dependence - cells from tumor break off and go into different systems/parts of the body (brain, blood, other organs) 4) cancer cells may survive and establish a new tumor in another part of the body

Question 50

Proto-oncogenes

Answer 50

- encode proteins that are involved in normal cell regulation

Question 51

Oncogenes

Answer 51

- if a proto-oncogenes get mutated, they become an oncogene oncogenes = potentially cancer-causing genes

Question 52

Proto-oncogene --> Oncogene

Answer 52

1) point mutation: - the oncogene would now be hyperactive or a degradation-resistant protein in normal cells: need growth factor to bind to receptor for the transduction pathway to start and then for normal cell division the oncogene -- the protein now is hyperactive so no growth factor is needed to bind to the receptor - the cell goes through the transduction pathway and divides with the signal on 2) Gene Amplification - mistake in meiosis or DNA Replication - now there's multiple copies instead of one copy of the gene - bc there's multiple copies of the gene, you make more proteins which can stimulate more receptors to tell the cell to divide more 3) Translocation - the gene moves to a new position under new controls - there's a new promoter - normal growth-stimulating protein is in excess

Question 53

Her2 proto-oncogene

Answer 53

normal cell: - normal amount of Her2 - cells grow and divide normally her2 postive cancer cell: - more receptors in their cell membranes - now the cell divides more - cells grow and divide fast because of amplification - there's too much Her2 targeted chemo: - blocks the receptor - now the cells won't divide excessively - can't block all of the receptors, only some of them

Question 54

Tumor Suppressor Proteins

Answer 54

they shut down cell division if conditions aren't favorable - if tumor suppressor proteins get mutated, the cell cycle checkpoints get ignored and damaged cells divide and divide

Question 55

BRACA1 and BRACA2

Answer 55

the tumor suppressor genes work to protect DNA damage during DNA Replication - helps repair damaged DNA at G2 checkpoint (now we have intact DNA) - it recognizes DNA damage and recruits repair enzymes

Question 56

P53

Answer 56

tumor suppressor - regulates cell damage and cell cycle abnormalities - p53 gets activated and decides to either fix the damage or it will send the cell into apoptosis - if p53 gets mutated, damaged DNA and cells will go thru mitosis

Question 57

How Does Tumor Suppressor Function get Messed Up?

Answer 57

- mutation - virus - epigenetic changes ex: HPV - HPV gets into your cell and uses its transcription and translation to make its HPV proteins - a tag (E6) can attach to P53 and it tells the cell to dispose of P53 - then P53 gets degraded, so the cell goes crazy without it

Question 58

Tumor Suppressors and Abnormal Methylation

Answer 58

tumor suppressor genes can be silenced by abnormal methylation - if there's hyper-methylation, the gene is off and no tumor suppressor is made ex: p53 isn't made even tho the sequence is correct ex: if the BRACA2 gene is hyper-methylated, the person will be more susceptible to breast cancer **Epigenetic Phenomenon

Question 59

Telomerase and Cancer

Answer 59

telomers: - ends of chromosome - shorten with each cell division - after around 10 divisions, the cell dies Telomorase maintains telomere length so the chromosomes don't shorten - cells that over express telomerase are immortal - telomerase activity detected in almost all human tumors **we want to get rid of telomerase in cancer cells

Question 60

RNAi (RNA Inhibition)

Answer 60

RNAi = single stranded nucleic acid complimentary to normal mRNA molecule made by the cell - when an anti-sense molecule and telomerase hybrid happens, translation can't happen - translation can't happen bc of telomerase mRNA/anti-sense hybrid

Question 61

Traditional Chemotherapy

Answer 61

traditional chemo = injections of chemicals into the blood stream to kill dividing cells - some prevent mitosis and some stop DNA Replication - these therapies are non-selective, only selective for rapidly dividing cells, but not selective for cancer cells - they don't allow the cell to go thru the cell cycle

Question 62

Radiation Therapy

Answer 62

high energy particles damage DNA - the cells get destroyed or injured - now it's specifically targeted to certain parts of the body

Question 63

Model of Cancer Development

Answer 63

- having one mutation usually doesn't lead to cancer **most cancers require multiple mutations - they need multiple mutations bc the cells have to reach checkpoints and they usually catch the mutation. There needs to be multiple mutations to be able to get past a checkpoint and not get caught

Question 64

Centrosomes

Answer 64

Microtubule organizing center