20. PROOFREADING

Question 1

1. When can Replication errors occur?

Answer 1

• they can occur during DNA replication
• EG: errors in base pairing

Question 2

2. What is Proofreading?

Answer 2

• it corrects errors during DNA replication

Question 3

3. How does Proofreading work?

Answer 3

• DNA Polymerase proofreads newly made DNA
• it then replaces any incorrect and mis-paired
  nucleotides

Question 4

4. What does DNA Polymerase have?

Answer 4

• it has a 3’-5’ exonuclease activity
• this mediates proofreading during replication

Question 5

5. What are two other types of DNA damage?

Answer 5

1. Exogenous
2. Environmental

Question 6

6. What are examples of Exogenous and Environmental factors that cause DNA damage?

Answer 6

1. Chemicals
   - EG: certain molecules in cigarette smoke
   : such as benzo-⍺-pyrene
2. Radiation
   • EG: UV Light, X-Rays, Radioactivity

Question 7

7. Does this diagram make sense?

Answer 7

• yes

Question 8

8. Name the 3 types of DNA repair mechanisms for single strand breaks?

Answer 8

1. Mismatch Repair (MMR)
2. Base Excision Repair (BER)
3. Nucleotide Excision Repair (NER)

Question 9

9. What is Mismatch Repair (MMR)?

Answer 9

• these are repair enzymes
• they correct any remaining errors in base pairing
  (these are known as mismatched bases)
• these commonly occur during DNA Replication
  (these are known as Replication errors)

Question 10

10. When does Mismatch Repair (MMR) occur?

Answer 10

• it occurs immediately after DNA Replication
• this is because most replication errors are detected
• these errors have been repaired by proofreading
  during Replication

Question 11

11. What is Base Excision Repair (BER)?

Answer 11

• this removes damaged bases
• these are caused by small non-helix distorting base
  lesions

Question 12

12. What is Nucleotide Excision Repair (NER)?

Answer 12

• this is the removal of bulky DNA lesions
• these are caused by Helix distorting
• an enzyme called nuclease will cut out and replace the
  damaged stretches of DNA

Question 13

13. What is on example of DNA lesions?

Answer 13

• Thymine dimers that are caused by UV light

Question 14

14. What is this diagram showing?

Answer 14

• Mismatch Repair
• (MMR)

Question 15

15. What is this diagram showing?

Answer 15

• Base Excision Repair (BER)

Question 16

16. What is this diagram showing?

Answer 16

• Nucleotide Excision Repair (NER)

Question 17

17. What is this diagram showing?

Answer 17

• this is Xeroderma Pigmentosum
• this is an exampled of an impaired Nucleotide Excision
  Repair

Question 18

18. What kind of disorder is Xeroderma Pigmentosum?

Answer 18

• this is an Autosomal Recessive Genetic Disorder

Question 19

19. What causes Xeroderma Pigmentosum?

Answer 19

• it is caused by a mutation in the genes
• these genes encode for the NER Repair Enzymes
• these enzymes are responsible for repairing UV light
  induced DNA damage

Question 20

20. What does Ultraviolet (UV) light cause?

Answer 20

• it causes the production of Thymine dimers (T-T) in
  DNA
• the Nucleotide Excision Repair (NER) is a DNA repair
  mechanism that is normally able to repair this damage

Question 21

21. What is the issue with a patient that has Xeroderma Pigmentosum?

Answer 21

• the NER DNA repair mechanism is inactive
• this makes the individual highly susceptible to skin
  cancers
• such as Melanoma

Question 22

22. Make sure you learn this table well.

Answer 22

• yes sir 🫡

Question 23

23. What is the source of Mismatched bases?

Answer 23

• replication errors
• these lead to mismatched bases

Question 24

24. What is the Repair Mechanism for Mismatched bases?

Answer 24

• Mismatch Repair
  (MMR)

Question 25

25. What inherited repair disorder is a result of Mismatched Bases?

Answer 25

- Hereditary Nonpolyposis Colon Cancer (HNPCC)

Question 26

26. What is the source of the Chemical Modification of Bases?

Answer 26

- chemicals that can damage DNA bases EXAMPLES: - Alkylating agents - oxidative DNA damage - free radicals

Question 27

27. What is the Repair Mechanism for the Chemical Modification of Bases?

Answer 27

- Base Excision Repair (BER)

Question 28

28. What Inherited DNA repair disorder is a result of the Chemical Modification of bases?

Answer 28

- Colorectal Cancer - Gastric Cancer

Question 29

29. What is the Source of Bulky DNA adducts?

Answer 29

- Pyrimidine (Thymine) dimers (UVB Light) - intercalating chemicals (benzo-⍺-pyrene) - these all distort the double helix

Question 30

30. What is the Repair Mechanism for Bulky DNA adducts?

Answer 30

- Nucleotide Excision Repair (NER)

Question 31

31. What inherited DNA repair disorder is a result of Bulky DNA adducts?

Answer 31

- Xeroderma Pigmentosum (XP)

Question 32

32. What is the Source of Double Strand Breaks?

Answer 32

- Ionising Radiation - Radioactivity - X-Rays - Y-Rays NB: - these breaks are much more severe - they break the whole chromosome

Question 33

33. What is the Repair Mechanism for Double-Strand breaks?

Answer 33

- Homologous Recombination (HR) - Non-Homologous End Joining (NHEJ)

Question 34

34. What Inherited DNA repair disorders result from Double-strand breaks?

Answer 34

- BRCA1 and BRCA2 defects - these are both tumour suppressor genes - they cause cell cycle arrest MUTATIONS OF THESE GENES LEAD TO: - a predisposition to breast and ovarian cancer - as well as chromosomal translocations

Question 35

35. What is the Evolutionary Significance of Altered DNA Nucleotides?

Answer 35

1. the error rate after proofreading repair is low - it is not yet zero 2. DNA damage may be recognised and repaired

Question 36

36. What happens if there is a failure to repair the DNA damage?

Answer 36

- mutations can occur - these cannot be repaired