Cell determination and cell sequence

Question 1

What happens once a cell differentiates regarding mechanism for memory?

Answer 1

Once a cell differentiates it remembers this state even without any external inducing signal

Question 2

What are the two ways for the mechanism for memory?

Answer 2

Chromatin remodelling and positive feedback

Question 3

How does positive feedback work in terms of A and B?

Answer 3

Signal only affects A and is only required to start cycle between A and B
A and B can resume the cycle without signal

Question 4

What is the master gene regulator for melanocytes?

Answer 4

MITF is the master gene regulator for melanocytes

Question 5

What happens when MITF gene is homozygous?

Answer 5

When homozygous, the MITF gene causes loss of all melanocytes

Question 6

What happens to the eyes in the loss if melanocytes?

Answer 6

Eyes become small due to loss of pigmented retina

Question 7

What does + mean in genetics?

Answer 7

Means a normal gene

Question 8

What does - mean in genetics?

Answer 8

Means a mutant gene

Question 9

What does -/- mean in genetics?

Answer 9

Means both copies mutant

Question 10

What does waadenburg syndrome 2 cause?

Answer 10

Deafness due to loss of pigments in ear

Congenital patchy loss of pigment in skin

Question 11

Process of MC1R-cAMP signalling in melanocytes?

Answer 11

• MSH binds to MC1R on the membrane
• This activates Ad cyclase enzyme that form PKA which are cAMP-dependent
• CREB proteins are phosphorylated and activated by PKA
• These PCREB enter the nucleus and bind to CRE in gene promoter

This increases MITF in melanocytes via transcription

Question 12

How are melanocyte-specific genes activated?

Answer 12

• MITF is transcribed and translated
• Produces a MITF protein
• MITF acts as a transcription factor for transcription of MC1R

Specialised proteins are made

Question 13

How can melanocyte differentiation be turned on?

Answer 13

Melanocyte differentiation can be switched on by MSH and stabilised even without

Question 14

What are myogenic factors?

Answer 14

master gene regulators in skeletal muscle differentiation. Can bind to DNA and E proteins

Question 15

What are E proteins?

Answer 15

Widely expressed transcription factors

Question 16

What is ID1?

Answer 16

A protein in myoblasts. Strongly bind to E proteins but not DNA

Question 17

What is cell senescene?

Answer 17

Permanent cell growth arrest after extended cell proliferation

Question 18

What is cell senescene strongly implicated in?

Answer 18

Strongly implicated in symptoms of ageing

Question 19

What is cell senescene a defence against?

Answer 19

A major defence against cancer

Question 20

What is cell lifespan?

Answer 20

The total number of cell doublings a cell goes thorough before senescene

Question 21

What do cells sometimes have when they go into senescene?

Answer 21

Sometimes they’ve biological markers

Question 22

What are the biological markers which are present when the cell goes into senescene?

Answer 22

○ Many more lysosomes in comparison to normal cells

○ Protein p16 a cell cycle inhibitor

Question 23

What is a telomere

Answer 23

A hexamer sequence TTAGGG repeated 1000s of times at the end of the chromosome

Question 24

What part of DNA not replicated normally and why?

Answer 24

3’ ends of DNA not replicated normally because RNA primer has to bind beyond the part to be replicated

Question 25

What is required to maintain the length of the telomere?

Answer 25

Enzyme telomerase is needed to maintain the length of telomere

Question 26

What is telomerase?

Answer 26

A protein-RNA complex

Question 27

What does telomerase do?

Answer 27

Replicates telomeric DNA by reverse transcribing DNA from its own RNA

Question 28

What happens to telomeres as cells divide and why?

Answer 28

Telomeres shorten as cell divide because normal somatic cells don’t contain TERT

Question 29

How is replicative senescene triggered?

Answer 29

Triggered by telomeres getting to a particular short length

Question 30

Why are germ line cells immortal?

Answer 30

Germline cells are immortal as they have TERT so telomeres remain long and cells can divide forever

Question 31

What percentage of cancer cells have TERT and what does this result in ?

Answer 31

Approx 90% of cancer cells have TERT so divide uncontrollably

Question 32

What does telomere shortening switch on?

Answer 32

Switches on DNA damaging signalling
This turns on p53 and then
p21
This inhibits CDK1/2 resulting in an arrest in cell divison

Question 33

What does radiation, oxidative stress and DNA damage do?

Answer 33

○ P16 switched on which inhibits CDK4/6

RB is activated which inhibits E2F resulting in an arrest in cell division.

Question 34

What are the effects on ageing?

Answer 34

○ Telomere length (measured in blood cells), variable, but on average falls with age. Typically very short in people aged >100.
○ p16 and other senescence-associated proteins are expressed increasingly in ageing tissues.
○ Telomere length at birth varies between people: genetically linked to age at death.
○ Defective genes for telomerase subunits give syndromes with premature ageing and early death.

p16 (CDKN2A) locus also genetically associated with human senile defects – cardiovascular disease, frailty, type II diabetes, neurodegeneration, cancer.

Question 35

What do embryonic stem cells express?

Answer 35

Express TERT

Question 36

What are embryonic stem cells naturally?

Answer 36

Naturally immortal

Question 37

What type of cells are embryonic stem cells?

Answer 37

Totipotent though sometimes called pluripotent

Question 38

Do somatic stem cells have telomerase?

Answer 38

Have some, but not enough to make the cell immortal

Question 39

Shortening of telomeres in somatic stem cells compared to any other cell

Answer 39

Telomeres shorten less in somatic stem cells than any other cell however do shorten so most somatic stem cells do senesce gradually.