DNA Repair And Cancer

Question 1

Ataxia Telangiectasia

Answer 1

Neurodegenerative disease of cerebellum
Normal DNA Repair Pathway disrupted
Increased risk of cancer (radiation sensitivity0

Question 2

Types of DNA Damage/Breaks

Answer 2

Single Stranded Breaks
Double Stranded Breaks

Question 3

Single stranded breaks repairability

Answer 3

Easier too repair than double stranded breaks
Template strand still present to make complementary copy

Question 4

Double stranded breaks repairability

Answer 4

Harder to repair
Template strand not present to repair coding strand

Question 5

2 Sources for DNA damage

Answer 5

-Exogenous
-Endogenous

Question 6

Exogenous sources of DNA Damage

Answer 6

-Ionising radiation (X-Rays)
-Alkylating agents (Add alkyl group to base G meaning correct bonding can’t happen strand. Breaks
-Mutagenic chemicals
-Anti-cancer drugs
-Free radicals

Question 7

2 Types of DNA damage that lead to need for Base Excision Repair and Nucleotide Excision Repair Respectively

Answer 7

-Deamination ( Cytosine converted to Uracil)
-Dimerisation (Forms between 2 similar bases, Thymine when exposed to UV light)

Question 8

How can DNA Replication errors damage DNA?

Answer 8

Wrong DNA nucleotide/base pairs may be incorporated by DNA Polymerase enzyme

Question 9

Replication fork

Answer 9

The point at which DNA Helicase has unwound the DNA and DNA Polymerase has bound to start incorporating new nucleotides

Question 10

DNA Exonuclease

Answer 10

Proof reads newly replicated DNA
Cuts out incorrect base pairs at the end of the DNA strands

Question 11

Fork Slippage

Answer 11

When wrong number of repetitive sequence is copied (Extra nucleotide added onto new strand or template strand loops out so 1 nucleotide is missing in new strand)

Question 12

Diseases caused by fork slippage

Answer 12

Huntington Disease (Autosomal DOminant Inheritance)
Fragile X Syndrome

Question 13

Huntington’s disease

Answer 13

Polyglutamine (CAG) repeats in protein too many times triggering Huntingtons

CAG repeats cause neural degeneration of Basal Ganglia affecting movement

Short Tandem Repeats

Question 14

DNA Replication stress

Answer 14

Inefficient replication where rep fork slows, stalls , breaks

Question 15

General DNA Damage response mechanism

Answer 15

Damage DNA activates signal
Detected by sensors
Sensors activated transducers
Transducers activate effectors which try and correct the damage

Question 16

G2 Checkpoint importance

Answer 16

Temporarily halts cell to check if DNA has been replicated correctly and make any repairs

Question 17

Types of single strand break repair

Answer 17

-Nucelotide excision repair
-Base excision repair
-Mismatch repair

Question 18

Base Excision Repair Process

Answer 18

Deamination of C to U
Base removed from nucleotide
Baseless nucleotide removed from DNA Backbone
DNA Polymerase fills hole with correct nuclreotide
Gap sealed by DNA Ligase

Question 19

Nucleotide Excision Repair (Single Stranded break repairs) Main Problem that it tries to repair and the process

Answer 19

UV forming a Thymine dimer
Surrounding DNA opens to form bubble
Enzymes cut out damaged region from bubble
Polymerase replaces excised DNA
Lipase seals backbone

Question 20

Mismatch repair (singles stranded breaks)

Answer 20

MIsmatched base detected e.g G to T
Mispaired nucelotide and its neighbours cut out from new strand
Polymerase replaces new strand
Lipase seals gap in DNA Backbone

Question 21

The 2 Double Strand Break Repair mechanisms

Answer 21

-Non-Homologous End Joining
-Homology-directed repair

Question 22

What is the process of Non-Homologus End Joining (Double Stranded break repair)?

What is the problem with it?

Answer 22

Proteins recognise and bind to broken strands
Other proteins remove extra nucleotides that may be damaged (resection)
DNA Lipase seals DNA backbone (phosphodiester bonds)

Repaired DNA might not be identical to original DNA

Question 23

Homolgy Directed repair (Double strand break repair)

Answer 23

Protein complex removes DNA on either side of break (RESECTION)
Heteroduplex forms
D loop forms
Polymerase and ligase repairs the break

Question 24

What DNA repair process fails causing Lynch Syndrome?

Answer 24

Mutations in mismatch repair genes
Autosomal dominant inheritance
High risk of - colorectal, endometrial, gastric and ovarian cancer

Question 25

Xeroderma Pigmentosa (XP)

Answer 25

Inherited condition Genes involved in producing key proteins needed in DNA Repair pathway of Nucleotide Excision Repair People very vulnerable to UV radiation (UV Causes Thymine dimer to form)

Question 26

Xeroderma Pigmentosa cancer risk factor

Answer 26

Cells unable to repair damaged DNA so cancerous cells more likely to proliferate

Question 27

Intratumour Heterogenity

Answer 27

Not all cells in tumour are the same Different sections of cells in tumour called sub clones

Question 28

Intertumour heterogenity

Answer 28

Differences between different tumours

Question 29

Chemotherapy effectiveness against cancer

Answer 29

Tumours have intratumour heterogeneity Chemotherapy may work effectively against all but 1 of the sub clones (so tumour not fully killed) Chemo may cause a sub clones to mutate become a drug resistant sub clone (could be more aggressive)

Question 30

Problem with Non-Homologous End Joining Repair

Answer 30

If more than 2 DNA ends are near each other wrong ends could be joined together Short sequence of DNA often lost from broken ends changing gene sequence

Question 31

Genetic Redundancy

Answer 31

More than 1 gene has the same function E.g: Gene A and Gene B = same

Question 32

Synthetic lethality Strategies

Answer 32

Utilise Genetic Redundancy to target only cancer cells

Question 33

Synthetic lethality strategy mechanism

Answer 33

Chemicals in chemo target the healthy gene to destroy the healthy gene. The healthy cells have other healthy gene so will be fine. Cancerous cells will only have mutated gene left so cell is undergoes apoptosis

Question 34

PARP inhibitors and breast cancer

Answer 34

Utilises Genetic redundancy Either BRCA1or BRCA2 is mutated so the PARP inhibitor targets the healthy BRCA gene so cancer cells enter apoptosis

Question 35

What type of failed DNA repair mechanism causes Ataxia Telangiectasia?

Answer 35

Failed Homolgy Directed repair (double strand repair) Patients sensitive to UV

Question 36

What is the cell cycle?

Answer 36

A series of events that a cell undergoes while it grows and divides

Question 37

Interphase

Answer 37

G1, S, G2 Where a cell spends most of It’s time

Question 38

G1 (Growth Stage 1)

Answer 38

Cell prepares for DNA Replication Grows in size and makes more organelles, enzymes and proteins needed for new cells

Question 39

S (synthesis)

Answer 39

Where DNA replication takes place Ensures 46 Pairs of chromosomes are present/96 chromatids so when mitosis carried out cells are diploid

Question 40

G2 (Growth stage 2)

Answer 40

More growth Cell forms material to form the spindle

Question 41

Mitosis, Meiosis

Answer 41

Mitosis produces 2 genetically identical diploid daughter cells Meiosis produce 4 non genetically identical haploid daughter cells

Question 42

Cytokinesis

Answer 42

Cleaving of a cell to produce 2 new separate cells

Question 43

Cell cycle stages

Answer 43

G1, S, G2, Mitosis/Meiosis, Cytokinesis

Question 44

Cell cycle checkpoints

Answer 44

Regulate the stages of the cell cycle

Question 45

3 Cell cycle checkpoints

Answer 45

G1 Checkpoint G2 Checkpoint M (Metaphase) Checkpoint

Question 46

G1 Checkpoint

Answer 46

Are conditions appropriate for replication (S/SYnthesis)

Question 47

G2 Checkpoint

Answer 47

Checks if DNA has been correctly replicated

Question 48

M (Metaphase checkpoint)

Answer 48

Checks if spindle fibres correctly join at centromeres of chromosomes