DNA Damage and Repair

Question 1

What are the causes of DNA Damage?

Answer 1

Replication Errors
Chemicals
Radiation

Question 2

Fill out the following diagram about DNA repair mechanisms

Answer 2

Question 3

Chemical Damage
Types

Answer 3

Deamination
Depurination
Base Adducts
Base Alkylation

Question 4

Chemical Damage
What is Deamination?

Answer 4

Transition of C/G to T/A during replication

Question 5

Chemical Damage
Causes of Deamination

Answer 5

Nitrous Oxide
Spontaneous

Question 6

Chemical Damage
What is Depurination?

Answer 6

Hydrolysis of the N-glycosyl linkage producing a basic site in the DNA

Question 7

Chemical Damage
What is the effect of Depurination?

Answer 7

Deoxyribose lacking Adenine and Guanine bases

Question 8

Chemical Damage
What is produced when tobacco is burnt?

Answer 8

Benzo[a]pyrenes or Polycyclic Aromatic Hydrocarbons

Question 9

Chemical Damage
What is Benzopyrene converted to inside the body?

Answer 9

Epoxides

Question 10

Chemical Damage
What effect can Epoxides have on DNA?

Answer 10

Base Adducts: Form bulky attachment onto the DNA

Question 11

Chemical Damage
What happens when Epoxides are replicated?

Answer 11

DNA Polymerase replaces Adenine opposite Guanine instead of Cytosine

Question 12

Chemical Damage
What effect does Nitrosamine have on DNA?

Nitrosamine is produced by tobacco

Answer 12

Base Alkylation: Alkylation of Guanine which interferes with replication

Question 13

Physical Damage
Types

Answer 13

Ultraviolet Radiation
Ionizing Radiation

Question 14

Physical Damage
Effect of UV Radiation

Answer 14

Cross-links adjacent pyrimidines on same DNA strand forming pyramidine dimers

Typically, a dimer forms between two Thymines

Question 15

Physical Damage
Effect of Ionizing Radiation

Answer 15

Causes Double-Stranded Break

Question 16

Replication Errors
Types

Answer 16

Transition: Replacement of base with base of same category (i.e. purine with purine or pyramidine with pyramidine)
Transversion: Replacement of base with base of another category (i.e. purine with pyramidine or pyramidine with purine)

Question 17

When may Insertions and Deletions occur?

Answer 17

Insertions and Deletions: Non-homologous end joining
Deletions: Replication Errors

Question 18

What happens if DNA Damage occurs?

Answer 18

Apoptosis
DNA Mutation

Question 19

What are the stages of DNA Repair?

Answer 19

Removal of Damage
Replacement of Damage

Question 20

What are the types of DNA Damage Repair?

Answer 20

Mismatch Repair
Nucleotide Excision Repair
Base Excision Repair
Double Stranded Break Repair

Question 21

Mismatch Repair
What is replication mismatch?

Answer 21

Replication Errors escaping proofreading

Question 22

Mismatch Repair
Which protein is involved in mismatch repair?

Answer 22

Mut proteins

Question 23

Mismatch Repair
What are the steps of Mut protein activity?

Answer 23

Identify strand with mismatch
Repair procedure

Question 24

Mismatch Repair
What are the steps of mismatch repair?

Answer 24

Endonuclease removes mismatched nucleotides + additional nucleotides
Pol III fills gap using ssDNA
DNA ligase joins ends

Question 25

**Nucleotide Excision Repair** When is it used?

Answer 25

UV radiation forming DNA dimers

Question 26

**Nucleotide Excision Repair** Procedure

Answer 26

UV specific endonuclease identifies dimer Cleaves DNA segment containing dimer Gap filled using DNA polymerase and ligase

Question 27

**Base Excision Repair** When is Base Excision Repair used?

Answer 27

When bases are lost spontaneously Deaminated, Alkylated or Methylated

Question 28

**Base Excision Repair** Procedure

Answer 28

DNA Glycosylase cleaves nitrogenous base with damage Endonuclease cleaves sugar and phosphate Polymerase fills gap and ligase joins ends

Question 29

**Double Stranded Break Repair** What may cause double stranded breaks?

Answer 29

Ionizing Radiation Oxidative Free Radicals Chemotherapeutic Drugs

Question 30

**Double Stranded Break Repair** Types

Answer 30

Non-Homologous End Joining Homologous Recombination

Question 31

**Double Stranded Break Repair** What is Non-Homologous End Joining

Answer 31

Joining of two cut ends May cause mutation

Question 32

**Double Stranded Break Repair** What is Homologous Recombination?

Answer 32

Between Homologous Chromosomes Causes no loss of DNA as sister chromosome used as template Occurs in late S or G2 phase

Question 33

Examples of diseases caused by mutation in DNA repair genes

Answer 33

Breast and Ovarian Cancer Hereditary Nonpolposis Colorectal Cancer/Lynch Syndrome Xeroderma Pigmentosum

Question 34

**Mutation of Repair Genes** Breast Cancer

Answer 34

Mutation of BRCA1 and 2 genes increase risk

Question 35

**Mutation of Repair Genes** Lynch Syndrome

Answer 35

Mutations of Mut genes allowing accumulation of mutations Causes tumors in colon

Question 36

**Mutation of Repair Genes** Xeroderma Pigmentosum

Answer 36

Mutation affecting nucleotide excision repair pathway Causes sensitivity to UV light