DNA repair Flashcards

1
Q

What are mutagens

A

Chemical agents that alter dna bases

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2
Q

How can dna bases be altered

A

Oxidation

Deamination

Alkylation

UV radiation

X ray exposure

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3
Q

How is guanine altered via oxidation

A

A hydroxyl radical reacts with guanine a makes 8-oxoguanine

The H on the imidzole is replaced with c=o

This is bad because 8-oxoguanine pairs with adenine instead of cytosine

During replication this makes it so that one strand has a ga pair and the other has a AT base pair

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4
Q

What is cytosine deamination

A

The amino NH2 group is removed by hydrolysis (water coming in)

Replaced with c=o and makes nh3

Cytosine turns into uracil instead of cg it UA

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5
Q

What is adenine demaination

A

Changed adenine to hypoxanthine

Pairs with cytosine not thymine

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6
Q

What is 5 methyl cytosine demaination

A

5 methyl cytosine is where cytosine had methyl group on c5 (next to c=O)

It regulated gene transcription

If demaination it turns into thymine and pairs with A

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7
Q

What base is deamination most unlikely for

A

Thymine

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8
Q

What is guanine alkylation

A

Adding a hydrocarbon to the base

First alfatoxin b1 reaction with cytochrome p450 to make aflatoxin B epoxied

aflatoxin B epoxide is reactive and reaction with the guanine in dna

It alkylates N7 of guanine and makes gc. To TA

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9
Q

What is a thymine dimer

A

When Uv light covalenty links adjacent (next to each other) pyrimidines along the dna strand

This causes a pyrimidines dimer where a bulge is formed and alters the DNA structure, causes a kink

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10
Q

What are approximate repairs and apoptosis

A

When it’s not possible to fix the error completely and restore the original information

The cell does approximate repairs or programmed cell death

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11
Q

What are the steps for repair

A

Recognizing the damage

Removing the damaged section

Repair (filling in where you removed with the proper thing)

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12
Q

What is mismatch repair

A

A base is match wrong during replication

This mismatch is recognized by MutS

This causes MutL to bind and recruits MutH

MutH endonuclease cleaves around the mismatch

exonuclease cuts out the incorrect base and backbone with it

DNA pol 111 fill the gap

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13
Q

How the the mismatch repair machinery know which strand on the dna has the incorrect base

A

The adenines in the template strand of the dna is methylated but the newly synthesized stand isn’t

The methylated strand is then seen as the correct sequence and it cleave off the opposite strand

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14
Q

What is direct repair

A

It was discovered in ecoli, mammals don’t use this

It repairs the site of pyrimidines dimers without removing dna fragments from it

It does this by DNA photo Lyase doing photochemical cleavage of the dimers

The energy of the visible light breaks the dimers cyclobutane ring and keeps the bases separated

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15
Q

What is nucleotide excision repair

A

It was discovered in E. coli

This is how mammals repair thymine dimers

Protiens detect the distorined in the helix due to the dimer

The uvrABC excinuclease (cut out) cuts out the dna and two sites across the distortion

DNA pol 1 fill in the gap, and DNA ligase repairs the resulting small nick in the backbone

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16
Q

What is base excision repair

A

Occurs in modified bases

The defective base is flipped and faces out of the helix into a enzyme glycosylases active site (if cyctosine is deaminated its uracil, so a uracil glycosylase comes in)

The glycosidic bond between the base and backbone is cleaved . This forms an AP site where a base is missing

An ap endonuclease come in and nicks the back bone next to the missing base

Deoxyribophosphodiesterase removes the depxyribose phosphate back bone unit

DNA pol 1 inserts the correct nucleotide, ligase seals the strand

17
Q

Slide 24/25

A

Mechanism

18
Q

Why does dna use thymine instead of uracil which is in rna

A

Cytosine delaminates to uracil

Uracil base pairs with adenine

If uracil is already in the dna as a normal base, actual mutations to uracil won’t be detected as good

By using thymine instead of uracil, the cell can detect the product of cytosine deaminations