DNA Damage Flashcards

(64 cards)

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
Adenine and Cytosine bases, | – shifting a hydrogen atom
From amino to imino
26
Tautomers creates a
transition mutation
27
ROS species primarily base pairs with
guanine
28
ROS converts guanine to
8-hydroxyl guanosine (8-OHdG)
29
Purine (G) to Pyrimidine (T) change is called
transversion mutation
30
most common type of DNA damage caused by UV irradiation
Is thymine dimer
31
Thymine dimer
UV light attacks the two adjacent thymine bases and cross links between carbon atoms 5 & 6 positions of two adjacent thymine bases.
32
This causes the bending of the DNA and disrupts the bonding of these two thymine
with their complimentary adenine nucleotides.
33
Thymine dimers is also an example for
the structural damage of DNA
34
What are the different repair mechanisms available to correct the DNA damage ?
1. Base Excision Repair 2. Nucleotide Excision Repair 3. Mismatch Repair
35
Base excision repair corrects the altered base derived
from oxidative deamination in which amino group is converted into keto group.
36
Removal of uracil which was created by the spontaneous deamination of cytosine in the DNA is by
The enzyme uracil DNA glycolase
37
The backbone near the defect is cut by an
Endonuclease
38
The defect is filled by the action of 9
DNA polymerase 1
39
The strand is rejoins by
ligase
40
Removal of the thymine dimers that was induced by ultra violet light is by
Nucleotide excision repair
41
Recognition and cleavage of the damaged strand
UV specific endonuclease (uvrABC excinuclease)
42
Correction of mis-incorporated bases that arise during DNA replication by
Mismatch repair (mmr)
43
MutS recognize the mismatch and recruits
MutL
44
MutL then recruites
MutH → endonuclease
45
MutH
Cuts the DNA strand flanking the mismatch
46
chews all the nucleotides in the small DNA fragment (flanking mismatch site).
Exonuclease 1
47
Missense mutation
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
Histidine
CAT
49
Proline
CCT
50
Nonsense mutation
is a point mutation in a sequence of DNA that results in creation of a premature stop codon.
51
Glycine
CAG
52
Stop codon
TAG
53
Nonsense mutation
Short and incomplete protein product
54
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.
Frame shift mutation is point mutation
55
Defects in Nucleotide Excision Repair
Xeroderma pigmentosum (XP)
56
Rare autosomal recessive disease
Xeroderma pigmentosum
57
Xeroderma pigmentosum patients
Are photosensitive and susceptible to skin cancer
58
Xeroderma pigmentosum is due to
Defect in the nucleotide excision repair of the damaged DNA
59
Defects in Base excision repair
Ataxia-telangiectasia
60
degenerative motor condition caused by failure to repair oxidative DNA damage in the cerebellum.
Ataxia-telangiectasia
61
It is a rare inherited disorder due to mutation in Ataxia-telangiectasia mutated (ATM) gene which is a part of base excision repair system
Ataxia-telangiectasia
62
It also affects the immune system, and other body systems.
Ataxia-telangiectasia
63
Defects in Mismatch repair system
Hereditary Nonpolyposis Colon Cancer
64
Hereditary Nonpolyposis Colon Cancer
mutations in the genes encoding for mismatch repair system, which fails to correct the repair