Damage, Repair and Recombination

Question 1

What are the forms of DNA damage?

Answer 1

Deamination
Depurination
Pyrimidine dimers
DMA breaks

Question 2

Types of DNA repair mechanisms

Answer 2

1) Base excision repair
2) Nucleotide Excision repair
3) Homologous recombination machinery

Question 3

What is the most frequent spontaneous form of DNA damage?

Answer 3

Hydrolytic depurination and deamination of bases

Question 4

What is depurination?

Answer 4

Releases guanine and adenine from DNA

Question 5

What is deamination?

Answer 5

Converts cytosine to an altered DNA base, uracil

Normally takes place in double helical DNA

Question 6

Base Excision Repair repairs what?

Answer 6

Depurination

Deamination

Question 7

Describe the steps of how deaminated or depurinated bases are repaired

Answer 7

1) The damaged base is removed by DNA glycosylase
2) The sugar phosphate with the missing base is cut out by the action of apurinic/apyrimidic endonuclease and a phosphodiesterase
3) The gap is filled with DNA polymerase and DNA ligase
4) DNA polymerase extends the primer; template junction
5) DNA ligase seals the nick

Question 8

How can UV irradiation cause DNA damage?

Answer 8

Causes the formation of pyrimidine dimers which can arrest DNA replication or cause mis-reading of the DNA sequence by DNA polymerase
Pyrimidine dimers can form between C and T neighbours

Question 9

Describe the steps of nucleotide excision repair

Answer 9

1) Excision nuclease cleaves a single stranded DNA segment containing the defect
2) DNA helicase removes damaged segment
3) DNA polymerase extends primer:template junction
4) DNA ligase seals the nick

Question 10

Defective nucleotide excision repair machinery cause which disorder?

Answer 10

Xeroderma Pigmentosum

Question 11

What is the effect of xeroderma pigmentosum?

Answer 11

Renders patients extremely sensitive to light induced skin cancer by the sin

Question 12

Which genes are complicated in xeroderma pigmentosum?

Answer 12

XPA,XPC,XPD,XPF,XPG
These all encode proteins involved in the nucloetide excision repair pathway for the correction of UV induced DNA lesions

Question 13

Double stranded breaks usually occur due to what?

Answer 13

By ionising radiation-type of mutagen

Question 14

What are the two repair mechanisms used to repair double stranded breaks?

Answer 14

Non-homologous end joining

Homologous recombination

Question 15

What is non homologous end joining?

Answer 15

Enzymes alert to the production of fragmented DNA and they rapidly rejoin free ends of the chromosomes which are colse together
Vulnerable to sticking the wrong peices of DNA together as it doesnt take into account the fragments sequence

Question 16

What is homologous recombination?

Answer 16

Thought of as a last line of defence since single stranded breaks produced by Base Excision Repair are vulnerable to double stranded breaks
These structures are more prone to becoming a double stranded break

Question 17

Mutations in which homologous recombination machinery are linked to cancer?

Answer 17

BRAC2 = breast cancer
ATM = leukemia and lymphoma
FANC = leukemia