Cell determination and cell senescence

Question 1

Positive feedback mechanism

Answer 1

1. Signal causes A to be made or activated
2. A causes B to be made or activated
3. B causes A to be made or activated
4. Once the signal stops the cycle keeps going

Question 2

Melanocyte differentiation

Answer 2

1. MSH-MC1R signalling causes cAMP to be made
2. cAMP causes MITF to be made via CREB activation
3. MITF causes cAMP to be made via MC1R transcription due to basal activity

Question 3

What are master gene regulators in skeletal muscle differentiation

Answer 3

Myogenic factors; MYOD1, MYF5, MYOG and MRF4

Question 4

What are E proteins

Answer 4

Widely expressed transcription factors that work as dimers with myogenic factors

Question 5

what is ID1

Answer 5

A protein in myoblasts that strongly binds to E proteins but not DNA, therefore acting as inhibitors to differentiation

Question 6

What happens to activate the muscle-specific gene

Answer 6

MYOD1 and E protein form a dimer that can bind to the gene promoter of DNA

Question 7

How is differentiation inhibited in myoblasts

Answer 7

ID1 and E proteins bind forming a dimer that cannot bind to the DNA promoter, therefore preventing the activation of that gene, preventing differentiation

Question 8

Cell senescence define

Answer 8

Permanent cell growth arrest following extended cell proliferation

Question 9

What are the morphological changes that occur in senescent human fibroblasts

Answer 9

The edge of the cells are hard to see due to loss of lamins
Prominent nucleoli
Large flat cells

Question 10

What are the molecular markers present in senescent cells

Answer 10

Many lysosomal beta-galactosidase

Lots of protein p16 since its a cell-cycle inhibitor

Question 11

What is a telomere

Answer 11

1000’s of repeats of a hexamer sequence (TTAGGG) at chromosome ends that protects the chromosome from DNA damage and prevents chromosomes from fusing with other chromosomes

Question 12

What is telomerase and what is it required for

Answer 12

An RNA-dependant DNA polymerase

It maintains the telomere length

Question 13

What is the structure of telomerase

Answer 13

An RNA-protein complex, made of TERC and TERT.

Question 14

TERT

Answer 14

telomerase reverse transcriptase, the protein part

Question 15

TERC

Answer 15

telomerase RNA component, the RNA part

Question 16

Why do human somatic cell chromosomes shorten

Answer 16

TERT is not expressed

Question 17

Why are germline cells and cancer cells immortal

Answer 17

TERT is expressed so chromosomes maintain full length telomeres

Question 18

Telomere shortening cell senescence pathway

Answer 18

1. Telomere shortening leads to DNA damage signalling
2. Tumour suppressor p53 gene expressed
3. Growth inhibitor p21 is made which inhibits CDK1 and CDK2
4. Cell cycle is arrested in G1 phase

Question 19

Radiation/DNA damage cell senescence pathway

Answer 19

1. DNA damage causes p16 to be expressed
2. p16 binds to CDK4 and CDK6 therefore cyclin D cannot form an active complex
3. pRB isnt phosphorylated so remains bound to E2F
4. E2F cannot promote the transcription of proteins required for the progression of the cell cycle
5. Cell cycle arrests in the G1 phase

Question 20

How do advanced cancer cells bypass cell senescence

Answer 20

They express TERT, and have p53 and p16 defects. This means the cell cycle wont be arrested so there will be rapid, uncontrolled divisions forming tumours

Question 21

How is cell senescence and ageing linked

Answer 21

Telomere length decreases in ageing tissues causing p16 to be expressed

Question 22

What is a master gene regulator

Answer 22

A master gene regulator is a transcription factor that co-ordinately regulates many/all of the specialised genes expressed by a particular cell type. It may not only positively regulate many genes but can also co-ordinately negatively regulate others.

Question 23

What is a master gene regulator in melanocytes

Answer 23

MITF