cell determination and cell senescence

Question 1

what is cell determination?

Answer 1

the ability to retain the memory of what they have differentiated into without the need for a continuous signal

Question 2

what is a master gene regulator?

Answer 2

a transcription factor that regulates many or all of the genes specifically expressed in a cell type.

Question 3

what is the mutation of one copy of MITF called in humans?

Answer 3

Waardenburg syndrome

Question 4

what are symptoms of waardenburg syndrome?

Answer 4

white patches on skin and hair and loss of pigment in the iris (melanocytes)

Question 5

what is the cell lifespan?

Answer 5

the total number of doublings that a cell population goes through before senescence.

Question 6

what do dividing fibroblasts look like?

Answer 6

long and thin

Question 7

what do senescent fibroblasts look like?

Answer 7

the edge of the nucleus is hard to see due to lamin loss

Question 8

what is an example of a molecular marker that indicates that the cell is senescent?

Answer 8

→lysosomal marker - beta galactosidase

→Protein P16 - a cell cycle inhibitor

Question 9

what are telomeres?

Answer 9

1000s of repeats of the sequence TTAGGG at the end of a chromosome

Question 10

why can the ends of linear DNA not be replicated?

Answer 10

the RNA primer has to bind beyond the part to get replicated

Question 11

When is replicative senescence triggered?

Answer 11

when the telomeres get short e.g 1-5 telomeres

Question 12

why are germline cells immortal?

Answer 12

they express TERT

Question 13

what is telomere length linked with?

Answer 13

age at death

Question 14

how does p53 work?

Answer 14

the ATM proteins scan the DNA for damage and activate the p53 which activates p21 which codes for proteins that arrest cell division at G1

Question 15

why do older people show decreased immunity?

Answer 15

their bone marrow stem cells cannot divide as much

Question 16

what are two examples of positive feedback in master gene regulators in differentiation?

Answer 16

→Melanocytes
→MITF (MIcrophthalmia-associated Transcription Factor) -
→Skeletal Muscle
→MYOD1 family

Question 17

how does the positive feedback of melanocytes happen?

Answer 17

→ MITF gene gets translated into the MITF protein

→which produces specialized proteins one of which is MC1R (melanocortin 1 receptor)

→ MSH (melanocyte-stimulating-hormone) binds to MC1R

→ activates cAMP

→activates PKA

→PKA then phosphorylates CREB and activated it to transcribe more MITF genes.

Question 18

what are E-Proteins?

Answer 18

→widely expressed as transcription factors and the myogenic factors work as dimers with E proteins.

Question 19

what is ID-1?

Answer 19

→(inhibitor of differentiation) it is an inhibitory protein found in myoblasts which are migrating cells in the embryo

Question 20

what are the myogenic factors?

Answer 20

→MYOD1
→MYF5
→MYOG
→MRF4.

Question 21

what are myogenic factors?

Answer 21

→master gene regulators in skeletal differentiation.

Question 22

what is the situation in normal skeletal muscle and in myoblasts expressing ID-1?

Answer 22

NORMAL MUSCLE
→MYOD1, MYF5, etc. bind and activate muscle gene promoters, working as dimers with E-proteins.

MYOBLASTS
→ID1 bind strongly to E-proteins, and prevents activation.
→ID1 has no DNA-binding domain. So ID1 inhibits differentiation.

Question 23

how do the MYOD regulators work in differentiation in the embryo?

Answer 23

→In migrating myoblasts MYOD1 and MYF5 are present but they are not able to work because of the IDI which blocks the MYOD from binding to the E protein.

→When the myoblasts get to their designated place, there are less growth factors such as FGF and IGF

→this destabilizes the ID 1 so the MYOD1 and the MYF5 are able to work because the ID1 has degraded.

→They promote each other’s transcription and bind with the E proteins and stimulate transcription.

→the change in environment destabilizes the inhibitor

→ myogenic factors are now free to bind and make dimers (active complexes) with the E-proteins.

→these go on to activate different muscle genes, .

Question 24

what is cell senescence?

Answer 24

→permanent cell growth arrest, following extended cell proliferation.

Question 25

what is telomerase and how does telomerase work?

Answer 25

→The enzyme telomerase, a protein-RNA complex

→replicates telomeric DNA by reverse-transcribing DNA hexamers (TTAGGG) from its own RNA sequence, and joining them to the chromosome end.

Question 26

what are TERT and TERC?

Answer 26

→TERT: telomerase reverse transcriptase (the protein part, = catalytic subunit).
→TERC (or TR): telomerase RNA component

Question 27

what are the mechanisms of cell senescence?

Answer 27

→The telomeres shorten
→The DNA damage signal phosphorylates p53 (a tumour suppressor), activating it
→ The p53 stimulates the expression of p21 (a growth inhibitor)
→P21 inhibits CDK 1/2/4/6
→That means that there is no phosphorylation of pRB, meaning that it remains bound to E2F, blocking transcription, thus effectively arresting cell division.

→ Radiation, oxidative stress or DNA damage occurs.
→ This activates p53 (and that continues down the same path as before) and p16
→P16inhibits CDK 4/6
→ That also continues down the same path as before.

Question 28

what are the three types of stem cell?

Answer 28

→Unipotent - one functional cell type
→Pluripotent - several cell types
→Totipotent - all cell types including placental cells.

Question 29

what type of cell is totipotent?

Answer 29

→inner cell mass of the embryo are totipotent stem cells called embryonic stem cells.

Question 30

what are some signs of ageing associated with stem cells?

Answer 30

→Older people show decreased immunity because their bone marrow stem cells cannot divide as much.

→Hair greying is linked to decreased melanocyte stem cells

→Skin healing decreases with age because of senescence in dermal fibroblasts.

→Epidermal stem cells have very little telomere shortening and are able to divide throughout life.