Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Semester 1 - MCBG > 10. DNA repair and cancer > Flashcards

10. DNA repair and cancer Flashcards

1
Q

What are the two types of DNA damage?

A
  1. Single strand damage

2. Double strand damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Which type of damage is more severe?

A

Double strand damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What happens to most of the damaged DNA?

A

They are recognised by the cell and repaired

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What happens when damage DNA is not recognised?

A

Results in a mutation - change in DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What happens when damaged DNA is recognised but cannot be repaired by the DNA repair mechanisms?

A

Results in a mutation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the 5 Exogenous sources that can cause DNA damage?

A
  • Ionising radiation
  • Alkylating agents
  • Mutagenic chemicals
  • Anti-cancer drugs
  • Free radicals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the majority (50%) of the ionising radiation we get from?

A

Radon gas from the ground

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Give 5 examples of where free radicals can be found

A
  1. UV light
  2. Mitochondrion
  3. Ionising radiation
  4. Smoking
  5. Air pollution
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are two endogenous sources of DNA damage?

A
  • Replication errors

* Free radicals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the 9 changes to DNA that causes damage?

A
  1. Apurinic site - location lacking a base
  2. Deamination - hydrolysis reaction of cytosine to uracil
  3. Mismatches - G pairs with T
  4. Pyrimidine dimer - two bases in the same strand connect
  5. Single strand breaks
  6. Double strand breaks
  7. Intercalating agent - chemicals between bases
  8. Interstrand cross links - cross links between two strands
  9. Bulky adduct - chemicals that bind to DNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is DNA replication stress?

A

Inefficient replication that leads to replication fork slowing, stalling and/or breakage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What 3 things can cause replication stress?

A
  • Replication machinery defects
  • Replication fork progression hindrance
  • Defects in response pathways
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Give an example of replication machinery defects?

A

DNA polymerase not working properly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

When DNA polymerase is not working properly, it can add a wrong base. What is the mismatch removed by?

A

3’ to 5’ DNA exonuclease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Five 6 examples of replication fork progression hindrance?

A
  1. DNA lesion
  2. ribonucleotide incorporation
  3. Fragile sites or oncogene-induced stress
  4. DNA secondary structure
  5. Repetitive DNA
  6. Transcription or RNA - DNA hybrids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How does repetitive DNA cause replication stress?

A

Repetitive DNA can lead to fork slippage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is backward slippage?

A

When there are repeats in DNA, the DNA polymerase may cause problems. When making the new strand it may cause the newly synthesised strand to loop out. This means one nucleotide is added to the new strand

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is forward slippage?

A

When there are DNA repeats the DNA polymerase may go too quickly that it causes the template strand to loop out. This means one nucleotide is omitted on the new strand

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is an example of a disease cause by backward slippage?

A

Huntington’s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Why type of disorder is Huntington’s?

A

Trinucleotide repeat disorders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the repeats in the gene that causes Huntington’s and what des it code for?

A

HTT gene has many CAG repeats which code for glutamine amino acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How many CAG repeats are found in a normal persona and a person with Huntington’s?

A

Normal 6-39 repeats

Disease 35-121 repeats

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the normal function of the protein that the HTT gene codes for?

A

Normal protein function still unknown

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What does the mutant version of the protein that is coded for by the HTT gene do?

A

Mutant protein aggregates in neurons

affecting mainly basal ganglia - lead to death of neuronesj

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What do we mean by defects in response pathways when talking about what causes replication stress?

A

When pathways that try to stop the replication fork progression hindrances don’t work properly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Describe the DNA damage response

A

When DNA damage or replication stress occurs, signals are picked up by sensors which sends signals to transducers that sends signals to effector proteins that bring about any of the 4 responses:
• Increased DNA repair - Increased transcription of DNA repair proteins
• Cell cycle transitions - to stop replication or division
• Apoptosis
• senescence - loss of a cell’s power of division and growth.

27
Q

What is the outcome If DNA damage levels too high or persist?

A
  1. Senescence - permanent cell cycle arrest

2. Apoptosis - cell death

28
Q

What is the DNA damage response in the ideal scenario?

A

repair DNA(proliferation) + maintain function

29
Q

What is the function of cell cycle checkpoints?

A

To check for defects that occur in the cell cycle and to allow Temporary arrest for DNA repair

30
Q

Where in the cell cycle are the 3 checkpoints found?

A
  1. G1 checkpoint - before entering s phase
  2. G2 checkpoint before entering mitosis
  3. Checkpoint in mitosis
31
Q

What is checked at the G1 checkpoint?

A

Is environment favourable?

32
Q

What is checked in the G2 checkpoint?

A

Is all DNA replicated?

Is all DNA damage repaired?

33
Q

What is checked in the checkpoint in mitosis?

A

Are all chromosomes properly attached to the mitotic spindle?

34
Q

What are the 4 different DNA repair mechanisms?

A
  1. Base-excision repair
  2. Nucleotide-excision repair
  3. Recombinational repair
  4. Mismatch repair
35
Q

When is base-excision repair used?

A

When there is deamination, an apurinic/abasic site or a single strand brea

36
Q

When is nucleotide excision repair used?

A

When there is bulky duct or pyrimidine dimer

37
Q

When is recombinational repair used?

A

When there are interstrand crosslinkss or double strand breaks

38
Q

When is mismatch repair used?

A

When there are mismatches

39
Q

What happens during base excision repair?

A
  1. Deamination converts cytosine base into uracil
  2. The uracil is detected and removed, leaving a baseless nucleotide
  3. The baseless nucleotide is removed, leaving a small hole in the DNA backbone
  4. The hole if filled with the right base by a DNA polymerase and the gap is sealed bu a ligase
40
Q

Describe the nucleotide excision repair

A
  1. UV radiation produces a thymine dimer
  2. Once the dimer has been detected, the surrounding DNA is opened to form a bubble
  3. Enzymes cut the damages region out of the bubble
  4. A DNA polymerase replaces the excised DNA and a linage seals the backbone
41
Q

What is the difference between base excision repair and nucleotide excision/mismatch repair?

A

In base excision repair, just the damaged base is removed. In nucleotide excision repair, as in the mismatch repair, a patch of nucleotides is removed.

42
Q

Describe what happens in mismatch repair

A
  1. A mismatch is detected in new strand
  2. The new DNA strands is cut and the mispaired nucleotide and its neighbours are removes
  3. The missing patch is replaces with correct nucleotides by a DNA polymerase
  4. A DNA ligase seals the gap in the DNA backbone
43
Q

What are the two types of double strand break repair?

A
  1. Non - homologous end joining

2. Homologous-directed repair

44
Q

Describe what happens in non-homologous end joining

A

In non-homologous end joining, the two broken ends of the chromosome are simply glued back together. Proteins protect the broken ends. The ends are brought together by enzymes and then joined together by ligase

45
Q

What is the disadvantage of non-homologous end joining?

A

This repair mechanism is “messy” and typically involves the loss, or sometimes addition, of a few nucleotides at the cut site.
So, non-homologous end joining tends to produce a mutation, but this is better than the alternative (loss of an entire chromosome arm)

46
Q

what happens in homologous directed repair?

A
  • In homologous recombination, information from the homologous chromosome that matches the damaged one (or from a sister chromatid, if the DNA has been copied) is used to repair the break.
  • In this process, the two homologous chromosomes come together, and the undamaged region of the homologue or chromatid is used as a template to replace the damaged region of the broken chromosome.
47
Q

What kind of model is cancer?

A

Multi step model

48
Q

What causes a normal cell to become premalignant and then malignant?

A

Mutation accumulation

49
Q

What can cause more mutations and thus stimulate carcinogenesis?

A

Replication stress

50
Q

What prevents carcinogenesis?

A

DNA damage responses

51
Q

Describe the structure of a tumour

A

Not made up of one clone, but many sub-clones(cell types)

52
Q

Where are mutations common in cancers?

A

In DNA repair factors

53
Q

What promotes tumour evolution?

A

Intra-tumour Heterogeneity

54
Q

What are the two problems that can occur in chemotherapy treatment?

A
  1. Differential sensitivity

2. Chemotherapy induced mutagenesis

55
Q

What is differential sensitivity?

A
  • chemotherapy may work well on a particular subclone so tumour goes down initially .
  • But if a particular subclone is resistant to chemotherapy, it can continue to grow and the cancer comes back
  • Chemotherapy therefore only treat part of the tumour
56
Q

What is chemotherapy induced mutagenesis?

A

• Chemotherapy promotes changes in the tumour -promote mutation of subclone to another powerful resistant subclone- cancer comes back

57
Q

Describe synthetic lethality strategies

A
  • Normal cells have two pathways and if one damaged, then other pathway still working
  • In cancer cells, one pathway has mutated, so treatment can target the other other pathway and stop it so that both pathways don’t work and cell dies
  • Doesn’t affect normal cells as the other pathway would work in normal cells
58
Q

What do PARP inhibitors do?

A

• Causes all single strand breaks to become double stand break which are more severe

59
Q

How can PARP inhibitors be used to treat breast cancer?

A

If we know that a tumour causes a repair mechanism which repair double-stranded breaks to become inactive we can use the PARP to turn all single strand breaks into double strand breaks so that the cancerous cell dies. The normal cells will be fine because they would have the repair mechanisms which fix double strand breaks.

60
Q

Why might there be a problem in producing the final Okazaki fragment in the lagging strand?

A

When the replication fork reaches the end of the chromosome and there is a short stretch of DNA that does not Get covered by an okazaki fragment. This is because the strand may be too short so the primer falls beyond the chromosome end. This would lead to parts of the DNA going uncooked in each round of replication leading to the strand getting shorter.

61
Q

What is present to prevent chromosomes getting shorter in each round of replication?

A

Telomeres

62
Q

What are telomeres?

A

Telomeres are repeats of the same short DNA sequence. • The repeats that make up a telomere are eaten away slowly over many division cycles, providing a buffer that protects the internal chromosome regions bearing the genes

63
Q

What enzyme reverses telomere shortening?

A

Telomerase

64
Q

How does telomerase work?

A

The enzyme binds to a special RNA molecule that contains a sequence complementary to the telomeric repeat. It extends (adds nucleotides to) the overhanging strand of the telomere DNA using this complementary RNA as a template. When the overhang is long enough, a matching strand can be made by the normal DNA replication machinery (that is, using an RNA primer and DNA polymerase), producing double-stranded DNA.

Semester 1 - MCBG (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions