Lecture 20: DNA Repair and Recombination

Question 1

How can DNA damage occur?

Answer 1

1. Spontaneous degradation
   a. Depurination reaction (base
   separates from sugar and
   phosphate)
   b. Deamination reaction (loss of an
   amino group - NH2 -), forms a
   different type of base, e.g., C to U
   so less easy to detect
2. Exogenous damage:
   a. ionising radiation
   b. UV radiation
   c. Chemicals in environment
3. Endogenous damage
   a. intracellular production of chemicals
   (e. g., oxygen free radicals)
   b. Errors during DNA metabolism

Question 2

What are the different DNA repair systems for different types of damage?

Answer 2

1. Mismatch repair - mismatches
2. Base-excision repair - Abnormal bases
3. Nucleotide-excision repair f- DNA lesions
4. Direct repair - pyrimidine dimers
5. DSB repair - HR & NHEJ

Question 3

What are examples of hereditary cancers that are linked to mutations in DNA repair proteins?

Answer 3

1. MMR - hereditary nonpolyposis colon
   cancer
2. NER - xeroderma pigmentosum

Question 4

What is meant by direct reversal of DNA damage?

Answer 4

1. Photolyases use light energy to repair
   pyrimidine dimers
   a. not present in humans and placental
   mammals
2. “O^6-methylguanine-DNA
   methyltransferase repairs methylated
   guanine”
   a. single methyl transfer deactivates
   protein permanently (so not an
   enzyme)

Question 5

What is the importance of O^6-methylguanine-DNA methyltransferase for removal of methyl groups from methylated guanine?

Answer 5

1. Removal is important because O^6- 
   methylguanine prefers to pair with T    
   (not C)
2. If not removed may lead to; GC to AT 
    mutations

METHYL GROUP ON O6; BLOCKING A HYDROGEN BOND

Question 6

What is the relationship between DNA repair and cancer?

Answer 6

1. Not repairing cell division pathways
2. Ionising radiation and chemotherapy
   works by inducing massive amount of
   DNA damage that can’t be repaired =
   apoptosis