Lecture 2 strobel: mutations, mutagens and dna damage repair part 2 Flashcards

(42 cards)

1
Q

What are mutagens?

A

chemical or physical agents that induce mutations

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2
Q

What do mutagens do?

A

alter DNA in different ways

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3
Q

What do chemical mutagens contain?

A

base modifiers, base analogs and intercalating agents

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4
Q

What are base modifiers?

A

they are chemical mutagens that covalently modify the structure of a nucleotides base

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5
Q

What do base modifiers do?

A

can disrupt pairing by alkylating bases

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6
Q

What are base analogs?

A

modified nucleotides that fool DNA polymerase and become incorporated into DNA during replication
* incorporation of base analogs can distort DNA structure
* some tautomerize at a high rate

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7
Q

What are intercalating agents?

A

they can be inserted into the DNA double helix between bases
* they directly interfere with DNA replication and it distorts the structure of the double helix

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8
Q

What are some examples of physical mutagens?

A

X-rays, gamma rays, ionizing radiation and UV light

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9
Q

What are induced mutations considered?

A

base modifiers

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10
Q

What is an example of a base analog?

A

5-bromouridine

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11
Q

What are some examples of base modifiers used during induced mutations?

A

nitrous acid and alkylating agents

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12
Q

What does nitrous acid do and how are humans exposed to it?

A
  • it replaces amino groups with keto groups (oxidative deamination)
  • it is formed in our stomach from nitrates that are used in smoked/cured meats
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13
Q

What do alkylating agents do?

A

covalently add ethyl or methyl groups to bases

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14
Q

What base does 5-bromouridine look like and what does it do?

A
  • thymine
  • it tautomerizes from the keto to the enol form at a high rate
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15
Q

What are the two general classes of radiation?

A

ionizing and non-ionizing radiation

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16
Q

List the characteristics of ionizing radiation.

A
  • includes x-rays and gamma rays
  • has short wavelength and high energy
  • can penetrate biological tissues
  • produces free radicals
  • can cause: deletions, oxidized bases, single strand nicks in DNA, crosslinking and double strand breaks in DNA
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17
Q

Wat are the characteristics of non-ionizing radiation?

A
  • has a longer wavelength and lower energy than ionizing radiation
  • its less penetrating but can still cause skin damage
18
Q

What are some examples of non-ionizing radiation sources?

A

sunlight, germicidal lamp and UV LED sample irradiator

19
Q

What can UV Light cause the formation of?

A

a DNA lesion called a thymine dimer

20
Q

Why do thymine dimers occur?

A

adjacent thymine bases become covalently linked, causing errors during DNA Replication

21
Q

What test do we use to tell if an agent is a mutagen?

A

the Ames Test

22
Q

What is the Ames Test?

A

a method foe assessing the mutagenicity of a physical or chemical agent

23
Q

What is the strategy for the Ames Test?

A

start with a salmonella strain that requires histidine to grow
* then expose the salmonella to a suspected mutagen
* if the agent is a mutagen it may cause reversion mutation that restores the ability to synthesize histidine

24
Q

What happens during direct repair?

A

an enzyme recognizes DNA dame=age and directly converts the damaged nucleotides back to the correct form

25
What occurs during excision repair?
a damaged base or nucleotide s removed from d=DNA, a segment of DNA in this region is excised and a new DNA strand is synthesized using the complementary strand as a template
26
What occurs during mismatch repair
similar process to excision repair but for mismatched normal nucleotides
27
How can damaged bases be removed and repaired?
by base excision repair
28
What enzymes are involved in base excision repair?
DNA N-glycosylases * primarily used for non-bulky lesions
29
What is an example of base excision repair?
the repairing of uracil in DNA
30
What are the 4 steps for repairing uracil in DNA?
1. uracil DNA glycosylase binds to the DNA that contains a U base 2. uracil DNA glycosylase then excises the U base yielding an AP site 3. an AP endonuclease site excises the AP site 4. DNA polymerase fills in the correct base, then DNA ligase seals the nick
31
Nucleotide excision repair of thymine dimers is used to repair what?
bulky lesions by excising a segment of DNA
32
What does Uvr C do?
makes 2 cuts on the DNA strand that contains the thymine dimer
33
What does UvrD do?
its a helicase that unwinds DNA
34
Defects in nucleotide excision repair cause what condition?
xeroderma pigmentosum which is characterized by a severe sensitivity to sunlight and predisposes someone to skin cancer
35
What are the factors that contribute to the fidelity of DNA replication?
base insertion, proofreading and mismatch repair
36
What is mismatch repair?
when systems correct base pair mismatches
37
Both bases involved in a mismatch are natural, how does the cell know which one is correct?
If the mismatch is due to an error in DNA replication, the new strand will contain the incorrect base. New DNA takes time to be methylated.
38
What 3 key proteins are used in the E. coli mismatch repair system?
MutS, MutL, and MutH
39
What does MutS protein do in the E. coli mismatch repair system?
finds a mismatch in DNA then binds to MutL which is a linker to MutH
40
What does MutH do in the E. coli mismatch repair system?
binds to hemi methylated dna and cuts the non-methylated DNA strand
41
What does MutU do in the E. coli mismatch repair system?
unwinds the DNA and an exonuclease degrades the new strand until just beyond MutS... this removes the incorrect base
42
What is the role of DNA polymerase in the E. coli mismatch repair system?
it fills in the gap and DNA ligase seals the nick