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CAN > L10: Maintenance Of Genomic Integrity > Flashcards

L10: Maintenance Of Genomic Integrity Flashcards

1
Q

How does DNA damage occur due to

A

Error in DNA replication
Spontaneous depurination
Exposure to agents e.g uv light, tobacco, ionising radiation

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2
Q

If we do not repair the damaged dna what can occur

A

Mutation that leads to cancer development

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3
Q

What are the 5 major dna repair mechanism

A

1) direct reversal damage
2) base excision by ROS deamination
3) nucleotide excision repair
4) homologous recombination repair and non homologous end joining
5) dna mismatch repair

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4
Q

What are the 3 different types of dna damage that can occur

A

7-methyl guanine
O-6alkyl guanine
Thymine dimers

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5
Q

How does 7-methyl guanine occur

A

A methyl group adds onto the guanine

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6
Q

What does 7-methyl guanine cause a problem with

A

DNA replication

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7
Q

How does a 0-6 alkyl guanine occur

A

A drug called ethyl methane sulphonate causes guanine to mutate to 0-6 alkyl guanine

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8
Q

What is the normal nucleotide paring

A

A-t

C-g

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9
Q

When we get a 0-6 alkyl guanine what nucleotide instead of cytosine (C) does it pair with

A

Thymine

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10
Q

What happen in the dna with 0-6 alkyl guanine during dna replication

A

Formation of AT pair rather than CG

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11
Q

Why does thymine diners occur

A

Due to uv light exposure

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12
Q

What are thymine diners

A

Formation of covalent bond between adjacent thymine in the dna

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13
Q

What does thymine diners cause a problem with

A

DNA replication

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14
Q

Broadly speaking what does dna repair involve

A
  • enzymatic reversal of the damage
    Or
  • Removal and replacement of the damage
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15
Q

With enzymatic reversal how are uv induced thymine reversed

A

Via monomeric action by action of visible light and photolyase (enzyme)

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16
Q

In enzymatic reversal how are 0-6 alkyl guanine reversed

A

Alkyl transferase remove the alkyl group on the guanine

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17
Q

In enzyme reversal how are strands breaks in sugar phosphate backbone reversed

A

By ligation

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18
Q

What are the substrates of base excision repair

A

1) spontaneous hydrolyic depurination of dna
2) deamination of cytosine
3) formation of dna adducts

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19
Q

Describe what happens in the base excision repair

A

1) altered dna base is excised from the dna by glycoslyase
2) this leaves an abasic site
3) apurinic site (sugar and phosphate) is removed
4) a new nucleotide is added and ligated via DNA ligase.

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20
Q

What are the type of dna that nucleotide excision repair works on

A

Double stranded DNA (not single stranded dna)

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21
Q

What does nucleotide excision repair notice

A

DNA distortions

22
Q

What can nucleotide excision repair remove

A

Thymine dimers

23
Q

Describe how nucleotide excision repair occurs when there are thymine dimers

A

1) thymine dimers are recognised by XPC and XPE
2) we then have the recruitment of TF2H complex that contains XPB and XPD proteins
3) XPA also binds to TF2H complex which verifies the damage
4) XPB and XPD are helicases which cause the unwinding of the dsDNA
5) XPF and XPG are then recruited which are nucleases that cut the sides of the DNA that contain the thymine dimers
6) polymerase then detects the gap and replaces the bases that were removed

24
Q

What is a daughter strand gap repair

A

When dna that has thymine dimers undergoes dna replication, gaps are left opposite the dimers as the dimers are not recognised.
DNA will gradually repair itself

25
Q

After the repair of the gaps does thymine dimers remain

A

Yes

26
Q

When are thymine dimers removed

A

Later by nucleotide excision repair

27
Q

What is xeroderma pigmentosum (XP)

A

An autosomal receives disorders where patients show excessive sun sensitivity

28
Q

What type of tumours does patients with XP show

A

Skin tumours

29
Q

Where does the skin tumours appear only at

A

Areas where skin is exposed to light

30
Q

What defect does XP patients have

A

Defect in DNA nucleotide exision repair

31
Q

Why do patient with XP have a defect in the dna exision repair

A

Defeats in the XP genes that are required for NER

32
Q

Name examples of XP genes that XP patients can show

A

XPA

XPC

33
Q

What defect does the XP variant of xerderma pigmentosum show a defect in

A

Replication of dna following exposure to uv light i.e daughter strand gap repair

34
Q

What happens in XP when the thymine dimers remix

A

Further mutation

35
Q

What gene can be further mutated due to unexcised thymine dimers

A

PTCH1 gene

36
Q

What does PTCH1 mutated gene cause

A

Basal cell naveous syndrome

37
Q

What are the 2 ways of repairing dna double strand breaks

A

Homologous recombination repair

Non homologous end joining

38
Q

What molecules does the homologous recombination repair involve

A

BRCA1

BRCA2

39
Q

When there is a double stranded dna break which module binds to the end of the breaks to protect it form damage

A

53BP1

40
Q

What is the role of BRCA1

A

Removes 53BP1

41
Q

Why does BRCA1 remove 53bp1 from the breaks

A

To promote resection and recombination to occur

42
Q

What molecule allows the recombination to occur

A

RAD51

43
Q

How is RAD51 brought to the right position

A

By BRCA2

44
Q

What other role does BRCA1 have

A

Cell cycle checkpoints

45
Q

What happens to the a cell that contains BRCA2 mutations

A

Cannot perform homologous recombination repair

46
Q

How do we treat BRCA2 deficient tumours

A

Use PARP inhibitor

47
Q

How does PARP inhibitors work

A

1) inhibit PARP which usually repair single stranded breaks
2) if you inhibit the single stranded break then it will form a double stranded break during DNA replication
3) with PARP inhibitors defect is made worse and leads to cell death

48
Q

When does dna mismatch usually occur

A

During dna replicaton

49
Q

What are the types of mismatchs that occur in dna

A

1) Base to base mismatch

2) insertion, deletion loops due to polymerase slippage during replication

50
Q

What does insertion and deletion loops give rise to

A

Micosatellites

51
Q

What does micro satellites lead to

A

Micro satellite instability

52
Q

What is the difference between a base and nucleotide

A

Nucleotide: a single unit of a polynucleotide chain made of sugar, phosphate group and nitrogenous base
Base: the type of nitrogenous base which is either a pyrimidine or purine (A,T,C,G)

CAN (25 decks)

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