gene expression

Question 1

What are stem cells?

Answer 1

*Undifferentiated / unspecialised cells capable of:
1. Dividing (by mitosis) to replace themselves indefinitely
2. Differentiating into other types of (specialised) cells

Question 2

Describe how stem cells become specialised during development

Answer 2

*Stimuli lead to activation of some genes (due to transcription factors - see 8.2.2)
● So mRNA is transcribed only from these genes and then translated to form proteins
● These proteins modify cells permanently and determine cell structure / function

Question 3

Describe totipotent cells

Answer 3

● Occur for a limited time in early mammalian embryos
● Can divide AND differentiate into any type of body cell (including extra-embryonic cells eg. placenta)

Question 4

Describe pluripotent cells

Answer 4

● Found in mammalian embryos (after first few cell divisions)
● Can divide AND differentiate into most cell types (every cell type in the body but not placental cells)

Question 5

Describe multipotent cells

Answer 5

● Found in mature mammals
● Can divide AND differentiate into a
limited number of cell types

Question 6

Describe unipotent cells, using an example

Answer 6

● Found in mature mammals
● Can divide AND differentiate into just one cell type

Example: unipotent cells in the heart can divide and differentiate
into cardiomyocytes (cardiac muscle cells)

Question 7

Explain how stem cells can be used in the treatment of human disorders

Answer 7

● Transplanted into patients to divide in unlimited numbers
● Then differentiate into required healthy cells (to replace faulty / damaged cells)

Question 8

Explain how induced pluripotent stem (iPS) cells are produced

Answer 8

1. Obtain adult somatic (body) cells (non-pluripotent cells or fibroblasts) from patient
2. Add specific protein transcription factors associated with pluripotency to cells so express genes associated with pluripotency (reprogramming)
   ○ Transcription factors attach to promoter regions of DNA, stimulating or inhibiting transcription
3. Culture cells to allow them to divide by mitosis

Question 9

Evaluate the use of stem cells in treating human disorders

Answer 9

For:
* can divide and differentiate into required healthy cells, so could relieve human suffering by saving lives and improving quality of life

• embryos are often left over from IVF and so would otherwise be destroyed.
• iPS cells unlikely to be rejected by patient’s immune system as made with patient’s own cells.

*iPS cells can be made without destruction of embryo and adult can give permission

Against:
*ethical issues with embryonic stem cells as obtaining them requires destruction of an embryo and potential life (embryo cannot consent)

*Immune system could reject cells and immunosuppressant drugs are required

*cells could divide out of control, leading to formation of tumours / cancer

Question 10

Examples of treatments using stem cells

Answer 10

● Potential treatment of Type 1 diabetes by creating healthy islet cells that produce insulin
● Bone marrow stem cell transplant for sickle cell disease / blood cancers
1. Destroy patient’s bone marrow before treatment → so no faulty cells are produced
2. Transplant stem cells from healthy person → divide and differentiate into healthy cells

Question 11

What are transcription factors?

Answer 11

● Proteins which regulate (stimulate or inhibit) transcription of specific target genes in eukaryotes
● By binding to a specific DNA base sequence on a promoter region

Question 12

Describe how transcription can be regulated using transcription factors

Answer 12

1. Transcription factors move from cytoplasm to nucleus
2. Bind to DNA at a specific DNA base sequence on a promoter region (before / upstream of target gene)
3. This stimulates or inhibits transcription (production of mRNA) of target gene(s) by helping or preventing RNA polymerase binding

Question 13

Explain how oestrogen affects transcription

Answer 13

1. Oestrogen is a lipid-soluble steroid hormone so diffuses into cell across the phospholipid bilayer.
2. In cytoplasm, oestrogen binds to its receptor, an inactive transcription factor, forming an oestrogen-receptor complex
3. This changes the shape of the inactive transcription factor, forming an active transcription factor
4. The complex diffuses from cytoplasm into the nucleus
5. Then binds to a specific DNA base sequence on the promoter region of a target gene
6. Stimulating transcription of target genes forming mRNA by helping RNA polymerase to bind

Question 14

Explain why oestrogen only affects target cells

Answer 14

Other cells do not have oestrogen receptors

Question 15

What is RNA interference (RNAi)?

Answer 15

● Inhibition of translation of mRNA produced from target genes, by RNA molecules eg. siRNA, miRNA
● This inhibits expression of (silencing) a target gene

Question 16

Describe the regulation of translation by RNA interference

Answer 16

*siRNA/miRNA binds to a protein,
*forms an RNA-induced silencing complex (RISC)
*single stranded miRNA / siRNA within RISC binds to target mRNA with a comp base sequence.
*leads to hydrolysis of mRNA into fragments which then degraded OR prevents ribosomes binding.
*reducing / preventing translation of target mRNA into protein

Question 17

Describe what is meant by epigenetics

Answer 17

● Heritable changes in gene function / expression without changes to the base sequence of DNA
● Caused by changes in the environment (eg. diet, stress, toxins)

Question 18

Describe what is meant by epigenome

Answer 18

All chemical modification of DNA and histone proteins - methyl groups on DNA and acetyl groups on histones

Question 19

To inhibit transcription

Answer 19

methylation increased and acetylation decreased

Question 20

Allow transcription

Answer 20

methylation decreased and acetylation increased

Question 21

Explain how methylation can inhibit transcription

Answer 21

1. Increased methylation of DNA - methyl
   groups added to cytosine bases in DNA
2. So nucleosomes (DNA wrapped around
   histone) pack more tightly together
3. Preventing transcription factors and
   RNA polymerase binding to promoter

Question 22

Explain how low acetylation can inhibit transcription

Answer 22

1. Decreased acetylation of histones
   increases positive charge of histones
2. So histones bind DNA (negatively
   charged) more tightly
3. Preventing transcription factors and
   RNA polymerase binding to promoter

Question 23

Describe how tumours and cancers form

Answer 23

● Mutations in DNA / genes controlling mitosis can lead to
uncontrolled cell division
● Tumour formed if this results in mass of abnormal cells
○ Malignant tumour = cancerous, can spread by metastasis
○ Benign tumour = non-cancerous

Question 24

Describe the function of tumour suppressor genes

Answer 24

Code for proteins that:
● Inhibit / slow cell cycle (eg. if DNA damage detected)
● OR cause self-destruction (apoptosis) of potential tumour cells (eg. if damaged DNA can’t be repaired)

Question 25

Explain the role of tumour suppressor genes in the development of tumours

Answer 25

● Mutation in DNA base sequence → production of non-functional protein ○ By leading to change in amino acid sequence which changes protein tertiary structure ● Decreased histone acetylation OR increased DNA methylation → prevents production of protein ○ By preventing binding of RNA polymerase to promoter region, inhibiting transcription ● Both lead to uncontrolled cell division (cell division cannot be slowed)

Question 26

Describe the function of (proto-)oncogenes

Answer 26

Code for proteins that stimulate cell division (eg. through involvement in signalling pathways that control cell responses to growth factors)

Question 27

Explain the role of oncogenes in the development of tumours

Answer 27

● Mutation in DNA base sequence → overproduction of protein OR permanently activated protein (Occur in non-coding regions like the promoter or enhancer sequences This can make the gene more active than normal → it’s transcribed more frequently) So more mRNA is made, leading to more protein being produce ○ By leading to change in amino acid sequence which changes protein tertiary structure ● Decreased DNA methylation OR increased histone acetylation → increases production of protein ○ By stimulating binding of RNA polymerase to promoter region, stimulating transcription ● Both lead to uncontrolled cell division (cell division is permanently stimulated)

Question 28

What is an oncogene

Answer 28

An oncogene is a mutated / abnormally expressed form of the corresponding proto-oncogene

Question 29

Suggest why tumours require mutations in both alleles of a tumour suppressor gene but only one allele of an oncogene

Answer 29

● One functional allele of a tumour suppressor gene can produce enough protein to slow the cell cycle OR cause self-destruction of potential tumour cells → cell division is controlled ● One mutated oncogene allele can produce enough protein to lead to rapid / uncontrolled cell division

Question 30

Explain the role of increased oestrogen concentrations in the development of some (oestrogen receptor-positive) breast cancers

Answer 30

*some breast cancers cells have oestrogen receptors, *If oestrogen concentration is increased, more oestrogen binds to oestrogen receptors, form more oestrogen-receptor complexes which are active transcription factors. 3. These bind to promoter regions of genes that code for proteins stimulating cell division. 4. This increases transcription / expression of these genes, increasing the rate of cell division

Question 31

Suggest how drugs that have a similar structure to oestrogen help treat oestrogen receptor-positive breast cancers

Answer 31

● Drugs bind to oestrogen receptors (inactive transcription factors), preventing binding of oestrogen ● So no / fewer transcription factors bind to promoter regions of genes that stimulate the cell cycle.

Question 32

Differences between malignant and benign tumours

Answer 32

*malignant- spread by metastasis - cells break off and spread to other parts of the body benign doesnt metastasise *mal- grow faster, ben slower *mal- cells have irregular nuclei, ben- normal, regular nuclei *mal- poorly differentiated/specialised, ben- well diffrentiated/specialised

Question 33

Where is oestrogen produced in women with menopause

Answer 33

the fat cells in the breast tissue

Question 34

Explain the relevance of epigenetics in cancer treatment

Answer 34

● Increasing DNA methylation OR decreasing histone acetylation of oncogene ○ To inhibit transcription / expression ● Decreasing DNA methylation OR increasing histone acetylation of tumour suppressor gene ○ To stimulate transcription / expression