DNA Damage Flashcards

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1
Q

Our DNA is under chemical and physical assault.

Name some of the common problems.

A

Ionizing Radiation

Spontaneous Depurination

Spontaneous Deamination

Thymidine Dimer Formation

Oxidation of Bases

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2
Q

What is Ionizing Radiation?

A

Breaking of phosphodiester linkages

Deletions of small segments of DNA from within a gene

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3
Q

What is Spontaneous Depurination?

A

Loss of purines from DNA (A and G)

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4
Q

Spontaneous Depurination

When a purine bass is lost, what is the site called?

A

Bond that holds purine bases to sugar is quite vulnerable to hydrolysis (A and G)

The loss of a purine case creates an APURINIC site (AP site)

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5
Q

What is the problem with an apurinic site?

A

The AP site has to be corrected or else the DNA cannot serve as a template o make DNA or RNA (because there is no nitrogenous base to pair with)

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6
Q

What is Spontaneous Deamination?

A

Removal of amino group from cytosine

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7
Q

What is the result of the removal of the amino group from cytosine?

A

If the amino group is removed from C, it produces Uracil.

If U remains, then it will serve as a template to add A (instead of G)

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8
Q

What is Thymidine Dimer Formation?

A

UV light causes production of thymine dimers

These dimers can occur when two T bases are adjacent to each other on the same strand

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9
Q

What is the consequence of thymidine dimer formation?

A

Thymine dimers can block DNA synthesis so they must be removed for a cell to divide.

Thymidine dimer formation happens all the time in sunlight.

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10
Q

What are the two diff systems for removing thymidine dimers?

A
  1. enzyme called photolyase recognizes thymine dimers with the help of a light absorbing chromophore breaks the covalent bond holding the dimers together, this restores both thymidine bases to their normal structure
  2. nucleotide excision repair system
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11
Q

True or False: Reactive oxygen species are by products of our aerobic metabolism.

A

True - Reactive oxygen species are by products of our metabolism.

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12
Q

What is an example of oxidation of bases?

Which base does this usually happen?

A

Addition of oxygen to our nucleotides

Usually happens in guanine

  • G can be transformed by an oxidizing agent into GO
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13
Q

Oxidation of Bases

Why does the GO base cause mutations?

A

The GO base, if left in the DNA, causes mutation because it can hydrogen bond quite well with adenine (instead of guanine’s normal partner cytosine - G and C).

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14
Q

What are two mechanisms of repair?

A

Base excision repair system

Nucleotide excision repair system

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15
Q

What are mutagens

A

Mutagens - chemicals/energy sources that raise frequency of mutation above naturally occurring frequency

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16
Q

How can we test for mutagenicity BEFORE humans etc are exposed to them?

In other words how do we identify chemicals that might be mutagens and not allow them to be in our foods, drinking water, etc.

A

AMES Test

17
Q

Describe the AMES test.

A
  • Ames took the rapidly growing bacteria, Salmonella
  • Control: WT that can make histidine
  • other strains where limitations are placed (can’t make histidine, removal of protective coat, knocked out several repair systems)
  • -> so we can measure reverse mutation (non-WT to WT)
18
Q

What are the major categories of mutagens?

A

High Energy Radiation

Base Analogs

Chemical Modifiers of otherwise normal bases

Intercalating agents

19
Q

MUTAGENS

Chemical Modifiers of otherwise normal bases

A

Hydroxylating agents

Alkylating agents

Deaminating agents

20
Q

MUTAGENS

What are Base Analogs?

A

These are compounds that resemble bases and can be incorporated into DNA.

But the incorporation can lead to incorrect DNA sequences being replicated.

21
Q

MUTAGENS

What are Intercalating Agents?

A

Intercalating agents are flat cyclical molecules that are roughly the same shape as a base pair.

They can stack in between base pairs.

22
Q

What are some DNA Repair Mechanisms?

A
  • Proofreading ability of DNA polymerases
  • Mismatch repair
  • Removal of thymidine dimers by photolyase
23
Q

DNA Repair Mechanisms

Removal of thymidine dimers by photolyase

A

Simplest system to remove thymidine dimers is with the enzyme photolyase

  • Photolyase bins to the thymidine dimer and w/ the help of chromophor molecule, it absorbs some of the energy form the sunlight and uses that energy to break the covalent bond linking the two thymidines (returning them to their normal state)
24
Q

Thymidine dimers readily form in _____.

So it is good to have two different repair systems to remove them. What are the two repair systems called?

A

Thymidine dimers readily form in sunlight.

25
Q

DNA Repair Mechanisms

Removal of thymidine dimers by photolyase

One other reversible repair system involves alkyltransferases.

A

One other reversible repair system involves alkyltransferases.

These enzymes search along the DNA and remove inappropriately added ethyl and methyl groups from the nitrogenous bases.

26
Q

DNA Repair Mechanisms

Removal of thymidine dimers by photolyase

What can Nucleotide Excision Repair fix?

A

Nucleotide Excision Repair can remove thymidine dimers AND other types of DNA damage.

27
Q

True or False: Nucleotide Excision Repair can only remove thymidine dimers. It is not useful in repairing other types of DNA damage.

A

False - Nucleotide Excision Repair can remove thymidine dimers AND other types of DNA damage.

28
Q

Nucleotide Excision Repair is good for detecting and removing ______

A

Nucleotide Excision repair is good for detecting and removing any type of DNA damage that distorts regions the DNA helix.

29
Q

Thymidine dimers, regions of mismatch, looped out sections of one strand of the helix or a distorted helix due to intercalating agents are all examples of _____

A

Helix distorting damage