DNA Mutagenesis: Mechanisms & Biological Relevance

Question 1

DNA mutation

Answer 1

Change in nucleotide sequence or rearrangement of genetic material

Question 2

Heritable mutations

Answer 2

• Organisms (parental germline)
• Viruses
• Can drive evolution

Question 3

Acquired mutations

Answer 3

Somatic cells (so not present in all cells of body)
-Can lead to cancer

Question 4

Types of mutation

Answer 4

• Silent
• Missense
• Nonsense
• Frameshift
• Gross change

Question 5

Mutations arise from

Answer 5

1) Misrepair of DNA damage

2) Spontaneous events

Question 6

Exogeneous sources of DNA damage

Answer 6

• Ionising radiation
• Alkylating agents
• UV light
• Anti-cancer agents
• Free radicals

Question 7

Endogeneous sources of DNA damage

Answer 7

• Free radicals

- Myosis

Question 8

Types of DNA base damage

Answer 8

• Mismatch
• Base modification
• Abasic site
• Bulky adduct
• Interstrand crosslink

Question 9

Types of DNA backbone damage

Answer 9

• Single strand break

- Double strand break

Question 10

Most common indirect DNA damage

Answer 10

Radiolysis of water

H2O -> free radicals

Question 11

Free radical

Answer 11

Highly reactive atom or molecule with single unpaired electron

Question 12

Effects of single-strand break

Answer 12

Little effect, relatively simple to fix

Question 13

Effects of double-strand break

Answer 13

• very difficult to fix
• Genotoxic: misrepair can cause gross structural changes
• Cytotoxic: no repair can be cytotoxic

Question 14

Intercalating agents

Answer 14

• Add or delete single nucleotide at replication

- Induce frameshift mutations

Question 15

Alkylating agents

Answer 15

• Very powerful mutagens
• Addition of alkyl group to DNA base
• Induces mispairing at replication
• Base substitution

Question 16

Result of replication fork slippage of newly synthesised strand

Answer 16

New strand has an extra nucleotide

Question 17

Result of replication fork slippage of template strand

Answer 17

New strand is missing a nucleotide

Question 18

Allele

Answer 18

Alternative form of the same gene

Question 19

SNP

Answer 19

Single nucleotide polymorphism (single base change in a particular form of a gene)

Question 20

Anonymous SNP

Answer 20

No known effect on gene

Question 21

Non-coding SNP

Answer 21

Outside gene

Question 22

Coding SNP

Answer 22

• Within Gene

- Can be synonymous (encode same aa as original) or non-synonymous (change aa sequence)

Question 23

CNV

Answer 23

‘Copy number variations’ (duplicates of same DNA segment)

Question 24

Achrondoplasia

Answer 24

Disorder of bone growth that causes the most common type of dwarfism

Question 25

Allosome

Answer 25

Sex chromosome

Question 26

Autosome

Answer 26

Chromosome that is not an autosome

Question 27

Cause of Huntington's Disease

Answer 27

Gene has CAG repeats (polyglutamine) -Normal gene, 6-39 repeats -Disease gene, 35-121 repeats Causes aggregates to form

Question 28

Intra-tumour heterogeneity

Answer 28

The observation that different tumour cells can show distinct morphological and phenotypic profiles within a tumour mass

Question 29

Hypervariable region

Answer 29

A region of a genome that is made up of a variable number of repeated sequences and is diagnostic for an individual

Question 30

Ames test

Answer 30

Widely employed method that uses bacteria to test whether a given chemical can cause mutations in the DNA of the test organism. More formally, it is a biological assay to assess the mutagenic potential of chemical compounds

Question 31

Reversion (mutation) frequency

Answer 31

Number of revertant colonies per total number of cells plated

Question 32

Mutation rate

Answer 32

Number of mutations per generation

Question 33

DNA damage from environment & normal metabolism

Answer 33

1x10^6 molecular lesions per cell per day

Question 34

DNA damage response: overview

Answer 34

Sensor proteins -> transducer proteins -> Mediators/effectors -> DNA repair OR cell cycle checkpoints/senescence/apoptosis

Question 35

Senescence

Answer 35

Temporary arrest (loss of a cell's power of division and growth)

Question 36

Apoptosis

Answer 36

Cell death

Question 37

Cell cycle checkpoint

Answer 37

Different stages during mitosis in which temporary arrest takes place (until DNA damage is repaired)