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Biochem > DNA Damage > Flashcards

DNA Damage Flashcards

1
Q

DNA damage can be either

A

structural or point mutation

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2
Q

When DNA damage occurs

A

the DNA repair system recognizes and corrects the damage

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3
Q

If the damage is not repaired

A

it will create a mutation during DNA replication.

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4
Q

What are the factors that cause replication-mediated mutagenesis ?

A

Endogenous factors

Exogenous factor

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5
Q

Endogenous

A

Spontaneous

Induced

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6
Q

Spontaneous

A
  1. DNA polymerase proof reading failure mediated errors
  2. Depurination mediated errors
  3. Deamination mediated errors
  4. Tautomers mediated errors
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7
Q

Induced

A

Natural metabolism that releases reactive oxygen species

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8
Q

Exogenous factor

A

UV irradiation mediated DNA damage

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9
Q

Proof reading in leading and lagging strand

A

3’-5’ Exonuclease activity of DNA polymerase III

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10
Q

RNA primer gap replaced by DNA fragment

A

3-5’ Exonuclease activity of DNA polymerase I

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11
Q

When DNA polymerase fails to correct error, the system that recognizes and corrects the errors

A

Mismatch repair system

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12
Q

the mismatch repair system fails to correct the error

A

During replication, the uncorrected mismatched nucleotides will create a permanent mutation in the genome

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13
Q

Depurination

A

refers to the loss of purines (guanine or adenine) from a nucleotide

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14
Q

Depurination occurs through

A

A spontaneous hydrolysis reaction

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15
Q

How does depurination induce mutation ?

A

DNA polymerase skips the depurinated site during replication and create a deletion mutation.

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16
Q

Deamination

A

refers to the loss of amino group (NH2).

It occurs due to spontaneous hydrolysis

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17
Q

Deamination of :

Cytosine ➡️

A

Uracil

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18
Q

Deamination of :

Adenine ➡️

A

Hypo-xanthine

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19
Q

Deamination of :

Guanine ➡️

A

xanthine

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20
Q

Deamination of :

5-methylcytosine

A

Thymine

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21
Q

Loss of amino group from methyl cytosine creates Thymine. If repair system fails to repair the thymine

A

it creates a transition mutation (cytosine to thymine) during replication.

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22
Q

Pyrimidine (C) to Pyrimidine (T) change is called

A

transition mutation

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23
Q

Tautomers

A

are nucleotide isomers that spontaneously interconvert by a chemical reaction called tautomerization.

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24
Q

Thymine and guanine bases shifting a hydrogen atom

A

From keto to enol

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25
Q

Adenine and Cytosine bases,

– shifting a hydrogen atom

A

From amino to imino

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26
Q

Tautomers creates a

A

transition mutation

27
Q

ROS species primarily base pairs with

28
Q

ROS converts guanine to

A

8-hydroxyl guanosine (8-OHdG)

29
Q

Purine (G) to Pyrimidine (T) change is called

A

transversion mutation

30
Q

most common type of DNA damage caused by UV irradiation

A

Is thymine dimer

31
Q

Thymine dimer

A

UV light attacks the two adjacent thymine bases and cross links between carbon atoms 5 & 6 positions of two adjacent thymine bases.

32
Q

This causes the bending of the DNA and disrupts the bonding of these two thymine

A

with their complimentary adenine nucleotides.

33
Q

Thymine dimers is also an example for

A

the structural damage of DNA

34
Q

What are the different repair mechanisms available to correct the DNA damage ?

A
  1. Base Excision Repair
  2. Nucleotide Excision Repair
  3. Mismatch Repair
35
Q

Base excision repair corrects the altered base derived

A

from oxidative deamination in which amino group is converted into keto group.

36
Q

Removal of uracil which was created by the spontaneous deamination of cytosine in the DNA is by

A

The enzyme uracil DNA glycolase

37
Q

The backbone near the defect is cut by an

A

Endonuclease

38
Q

The defect is filled by the action of 9

A

DNA polymerase 1

39
Q

The strand is rejoins by

40
Q

Removal of the thymine dimers that was induced by ultra violet light is by

A

Nucleotide excision repair

41
Q

Recognition and cleavage of the damaged strand

A

UV specific endonuclease (uvrABC excinuclease)

42
Q

Correction of mis-incorporated bases that arise during DNA replication by

A

Mismatch repair (mmr)

43
Q

MutS recognize the mismatch and recruits

44
Q

MutL then recruites

A

MutH → endonuclease

45
Q

MutH

A

Cuts the DNA strand flanking the mismatch

46
Q

chews all the nucleotides in the small DNA fragment (flanking mismatch site).

A

Exonuclease 1

47
Q

Missense mutation

A

is a point mutation (A to C) in which a single nucleotide change results in
a codon that codes for a
different amino acid.

48
Q

Histidine

49
Q

Proline

50
Q

Nonsense mutation

A

is a point mutation in a sequence of DNA that results in creation of a premature stop codon.

51
Q

Glycine

52
Q

Stop codon

53
Q

Nonsense mutation

A

Short and incomplete protein product

54
Q

which a deletion or insertion of nucleotides in a DNA sequence shifts the reading frame of the coding sequence that results in a completely different translation of protein sequence from the original protein.

A

Frame shift mutation is point mutation

55
Q

Defects in Nucleotide Excision Repair

A

Xeroderma pigmentosum (XP)

56
Q

Rare autosomal recessive disease

A

Xeroderma pigmentosum

57
Q

Xeroderma pigmentosum patients

A

Are photosensitive and susceptible to skin cancer

58
Q

Xeroderma pigmentosum is due to

A

Defect in the nucleotide excision repair of the damaged DNA

59
Q

Defects in Base excision repair

A

Ataxia-telangiectasia

60
Q

degenerative motor condition caused by failure to repair oxidative DNA damage in the cerebellum.

A

Ataxia-telangiectasia

61
Q

It is a rare inherited disorder due to mutation in Ataxia-telangiectasia mutated (ATM) gene which is a part of base excision repair system

A

Ataxia-telangiectasia

62
Q

It also affects the immune system, and other body systems.

A

Ataxia-telangiectasia

63
Q

Defects in Mismatch repair system

A

Hereditary Nonpolyposis Colon Cancer

64
Q

Hereditary Nonpolyposis Colon Cancer

A

mutations in the genes encoding for mismatch repair system, which fails to correct the repair

Biochem (8 decks)

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