Topic 10: DNA Repair And Cell Cycle

Question 1

What are the 4 different phases of the eukaryotic cell cycle?

Answer 1

G1
S
G2
M

Question 2

What is G1 phase?

Answer 2

Cell content duplication

Question 3

What is S phase?

Answer 3

DNA replication

Question 4

What is G2 phase?

Answer 4

Double check and repair

Question 5

What is M phase?

Answer 5

Mitosis

Question 6

What is G0 phase?

Answer 6

Stationary phase or quiescence (inactivity)

Question 7

What are 6 exogenous factors that can influence the integrity of DNA?

Answer 7

• Ionising radiation
• UV
• Alkylating agents
• Mutagenic chemicals
• Anti-cancer drugs
• Free radicals

Question 8

What are 2 endogenous factors that influence the integrity of DNA?

Answer 8

• Free radicals

- Replication errors

Question 9

What are 9 types of DNA damage that can occur?

Answer 9

• Apurinic site (missing base)
• Deamination (missing amino group)
• Mismatches (wrong base pair)
• Double strand breaks
• Pyrimidine dimer
• Intercalating agent (random molecule inserted)
• Interstrand cross link
• Single-strand break
• Bulky adduct

Question 10

What is replication stress?

Answer 10

Inefficient replication that leads to replication fork slowing, stalling or breakage

Question 11

What are the 2 ways that fork slippage causes mutations?

Answer 11

When there is repetitive DNA present, fork slippage can happen:

1. Backward slippage - newly synthesized strand loops out, one extra nucleotide is added
2. Forward slippage - template strand loops out, new strand missing one nucleotide

Question 12

How does fork slippage cause Huntington’s Disease?

Answer 12

Fork slippage can lead to trinucleotide expansion, CAG repeats in HTT gene leads to polyglutamine repeats in Huntington protein (>36 repeats)

Huntington proteins aggregates in neurons affecting mainly basal ganglia

Question 13

What is the DNA damage response?

Answer 13

DDR includes sensors to detect damage, transducers to send signals and effectors to repair damage.

If DNA damage levels too high or persist = senescence (permanent cell cycle arrest) or apoptosis (cell death)

If DNA damage levels are manageable = proliferation after DNA repair and cell cycle control

Question 14

What are the 3 DNA repair mechanisms?

Answer 14

Base-excision repair
Nucleotide-excision repair
Mismatch repair

Question 15

What is base-excision repair?

Answer 15

Uracil is detected and removed, leaving a base-less nucleotide, then base-less nucleotide is removed, and hole is filled with right base by DNA polymerase and gap is sealed by ligase

Question 16

What is nucleotide excision repair?

Answer 16

Dimer detected, surrounding DNA opened to form a bubble, enzymes cut out damaged region, DNA polymerase replaces DNA and ligase seals the backbone

Question 17

What is mismatch repair?

Answer 17

Mismatch is detected, new DNA strand is cut by endonuclease, mispaired nucleotide and its neighbors are removed by exonuclease, missing patch is replaced with correct nucleotides by DNA polymerase and ligase seals gap in backbone

Question 18

What is non-homologous end joining?

Answer 18

When double strand break occurs, broken ends are recognized and protected. Complex is formed and damaged ends are removed, then broken ends are lighted.

Error-prone

Question 19

What is homology-directed repair?

Answer 19

Using an intact DNA template to replicate and replace the broken parts of the DNA

Less error prone

Question 20

What is tumor heterogeneity?

Answer 20

Tumors contain diverse cells that have different molecular profiles and sensitivity to treatment

Question 21

What is cancer evolution?

Answer 21

When chemotherapy is used to treat heterogenous tumors,

There can be differential sensitivity because tumor is heterogenous, chemotherapy ineffective on some parts and it continues to undergo clonal expansion

There can be chemotherapy-induced mutagenesis, it makes some part of the tumor grow

Question 22

What is the relationship between mutations, DNA repair and cancer?

Answer 22

Mutations in DNA repair factors stimulate carcinogenesis, causing cancers