Mutations and Cancer

Question 1

Describe the types of Gene Mutations?

Answer 1

Addition/Deletion: complete loss/gain of a base in DNA, causes frame shift

Substitution: can cause silent mutation due to degenerate nature.

Inversion: segment of code is reversed.

Duplication: doubling of sequence base pairs so the resultant cells have more than 2 copies of every gene.

Translocation: when genes relocate to a non-homologous chromosome

Question 2

Describe the types of substitution mutation?
Silent: Missense: Nonsense:

Answer 2

Silent: Does not alter AA sequence, degenerate.

Missense: alters a single AA, eg SCD

Nonsense: Creates a premature stop codon, affecting structure and function of protein, eg CF.

Question 3

What are mutagenic agents? What do they do?

Answer 3

Mutagenic agents include X rays and gamma rays which damage the DNA molecule and chemicals that alter the DNA structure, or interfere with DNA replication.

mutation rate increase with the presence of mutagenic agents

Question 4

What is a totipotent cell?

Answer 4

Totipotent cells are cells that can divide into any type of body cell or whole organism

Question 4

Explain how cells lose their totipotency and become specialised:

Answer 4

Totipotent stem cells (first 3 divisions) can divide and produce any type of body cell.
ONLY for a limited time in early mammalian embryos (first 3/4 divisions).
During development cell specialisation occurs (some genes are switched on / off) and cells loss they totipotency.

Question 5

Describe the origins and types of stem cells. Explain the difference between totipotent, pluripotent, multipotent and unipotent

Answer 5

Toti: Differentiate into any cell type

Pluri: (embryonic), differentiate into any cell type bar the cells that form the placenta.

Multi: (Adult) Differentiate into a limited range of cell types.

Uni: Only Within their own cell type.

Question 5

What are induced pluripotent stem cells?

Answer 5

laboratory grown PLURIPOTENT cells that scientists have found can be produced from UNIPOTENT cells using certain protein transcription factors.

Question 6

Explain how pluripotent stem cells can be used to treat human disorders:

Answer 6

Using differentiation factors to produce colonies of different cell types.

1. Producing tissues for skin grafts.
2. Research into producing organs for transplant.
3. Research into how cells become specialised.
4. Research into cancer.
5. Research into serious disease and the use of stem cells to cure such diseases as Parkinsons disease

Question 7

What is small interfering RNA? How does small interfering RNA affect gene expression?

Answer 7

siRNA interferes with translation by binding to mRNA and cleaving it.

Enzyme converts RNA into Double stranded RNA.

Enzyme cuts Double RNA into siRNA.

One of the 2 strands binds with an enzyme to form the RNA-induced Silencing Complex (RISC).

siRNA has a comp base sequence to a specific section of mRNA.

siRNA guided the enzyme via complementary base pairing to this section.

Enzyme cuts mRNA into small sections, blocking gene expression

siRNA binds to target mRNA and the mRNA is hydrolysed into fragments by RNA hydrolase.

(ribosomes are prevented from attaching to the mRNA for miRNA)

Translation does not take place, polypeptide not produced and gene expression inhibited.

Question 8

Can you explain how oestrogen affects gene transcription?

Answer 8

Oestrogen is lipid soluble, passes through CSM into nucleus.

Binds to Complementary ER alpha receptor.

Receptor changes shape and is released from a protein complex.

Oestrogen receptor diffuses and binds (with a cofactor) to the promoter region stimulating RNA polymerase to transcribe the gene.

Question 9

Can you describe the nature of the epigenome?

Answer 9

Inheritable chemical tags that determine the shape of the DNA-histone complex.

Keeping genes tightly packed through methylation or loose through acetylation to prevent/cause transcription and translation of a gene.

Question 9

What is meant by epigenetics?

Answer 9

inheritable changes in gene function without changes to the DNA base sequences.

Question 10

Can you explain the effects of decreased acetylation of histones?

Answer 10

Histone molecules are the proteins the DNA is wrapped around,.

The side branches of these proteins
contain the amino acid leucine.

Less acetylation of leucine means the histones remain more tightly packed

Promoter and target gene are inaccessible to transcription factors and RNA polymerase

Gene stays switched off.

(Acetylation of histone tails reduces positive charge, reducing attraction to negative DNA)

Question 11

How is it thought that epigenetic inheritance takes place?

Answer 11

Changes to the epigenome are caused by changes in the environment such as smoking, stress, exercise and diet.

These changes are heritable so can influence the gene expression in offspring.

Question 11

Can you explain the effects of increased methylation of DNA?

Answer 11

Methyl groups added to Cytosine on C5 within CpG islands catalysed by methyltransferase.

This silences the affected genes by tightening the CpG islands

Making the promoter region on the target gene inaccessible to the transcription factor or RNA polymerase.

Gene remains switched off, not transcribed/translated.

Question 12

How could epigenetics and disease be linked? How might diseases be treated with epigenetic therapy?

Answer 12

Targeting epigenetic mechanisms to regulate methylation or acylation with drugs or other interventions.

Eg inhibiting methyltransferase.

Question 13

Can you distinguish between benign and malignant tumours?

Answer 13

Benign: Large, Sloe, Normal nucleus, specialised and well differentiated, only form primary tumours, surrounded by capsule to remain compact, less likely to be life-threatening, localised effects, removed surgically, rarely reoccur.

Malignant: Large, faster, nucleus is larger and darker due to abundance of DNA, Unspecialised, metastasise to form secondary tumours, no capsule so can grow finger-like projections into tissues, systemic causing fatigue and weight loss, removal included chemo and surgery, reoccur frequently.

Question 14

Can you explain the role of oncogenes and tumour suppressor genes in the development of tumours?

Answer 14

If a DNA mutation (/under methylated) occurs in a proto-oncogene, it alters to become an ONCOGENE. This results in an over-stimulation of cell division, so that cell division is permanently switched on. This results in a mass of cells known as a tumour.

Increased methylation of tumour suppressor genes
Mutation in tumour suppression genes
Tumour suppressor genes are not transcribed
Results in uncontrolled cell division
If a DNA mutation occurs in a tumour-suppressor gene, the gene becomes inactivated, so it stops inhibiting cell division, so the rate of cell division increases.

Question 15

Can you explain how increased oestrogen levels can cause breast cancer?

Answer 15

Oestrogen diffuses and binds to comp ERa.
Causes a change of shape in receptor
Detaches from complex
Binds to Promoter region on Proto-onco genes and activates RNA polymerase
Transcribes and translates gene increasing rate of cell division
Tumour develops.