Brainscape's Knowledge GenomeTM

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


See full index

MCD > DNA Damage & Repair > Flashcards

DNA Damage & Repair Flashcards

1
Q

Name the 5 types of DNA damage

A
  • Single-strand break
  • Double-strand break
  • Bulky adducts (a piece of DNA covalently bonded to a (cancer-causing) chemical)
  • Base mismatches (inc. insertions and deletions)
  • Base alkylation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Name the two causes of DNA damage, giving examples for each

A

Environmental Damage

  • Chemical (i.e. carcinogens) – chemical damage originates from a wide range of sources (dietary, lifestyle, occupational, medical [i.e. treatments – chemotherapy etc.])
  • Non-ionising radiation – UV
  • Ionising radiation – cosmic particles (sub-atomic particles), x-rays

Endogenous Damage (DNA damage is a natural phenomenon)

  • ROS
  • Spontaneous deamination
  • Replication errors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

List 5 potential consequences of DNA repair failures

A
  • Cancer
  • Neurodegeneration
  • Immune Dysfunction
  • Sterility
  • Ageing (Progeria)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the 3 major sources of chemical damage (to DNA)?

A
  • Hydrolytic Attack
  • Oxidative Damage
  • Alkylation
  • **Methylation **
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Outline the following types of hydrolytic attack on DNA? Explain any potential conseqences.

  • Depurination
  • Depyrimination
  • Deamination
  • Strand Breaks
A
  • Depurination – removal of a purine base (this does occur naturally/i.e. it is a normal physiological process).
  • Depyrimination – removal of pyrimidine base
  • **Deamination - **Cytosine Deamination: C –> U (remember U is normally only found in RNA). Can be reveseved (i.e. if the U is replaced with a C)
  • Strand Breaks
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Concerning Oxiative Damage:

(a) What is a conseuqence of free radicals?
(b) Name three types of oxidative damage and their effects.

A

(a) Free Radicals from normal metabolism attach purine and pyrimidine rings caused strand breaks
(b) There are over 100 oxidative modifications of DNA, examples include:

  • G –> 8-hydroxyguanin (therefore pairs with A instead of C)
  • Loss of planar ring (of bases) resulting in non-coding bases
  • Helical distortion – addition of covalent bonds between base and sugar-phosphate backbone (distorts the helix)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Methylation is an example of Alkalation - outline this process and discuss potential complications of G –> meG conversion.

A

Methylation

  • Distorts the DNA structure via alkylation (there are many environmental alkylating agents

Methylation of G: G –> meG

  • Consequences – methyl group distorts the DNA structure (can be corrected by dealkylation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is endogenous DNA damage?

A

Damage that is not due to chemical changes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

List and explain the two main types of endogenous DNA damage, give examples for each,

A

Replication Errors – consequence = mismatches or small loops (of bases) resulting in helix distortion

  • Nucleotide insertions/deletions
  • Incorporation of wrong nucleotide
  • Incorporation of damaged nucleotides

Radiation Damage – consequence = CPDs (cyclobutane pyrimidine dimers) resulting in helix distortion

  • Ionising radiation (cosmic rays and X-rays)
  • UV
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Name and briefly outline the 6 major DNA repair mechanisms

A
  • Direct Repair - Reversal of DNA damage
  • Base Excision Repair (BER) – removes single damaged base (main protector against metabolic damage)
  • Nucleotide Excision Repair (NER) - removes damaged nucleotides (particularly CPDs, thymine dimers and large chemical adducts)
  • Mistmactch Repair (MMR) – removes mismatched base pairs and insertion/deletion loops
  • Homologous Recombination Repair (HR) – double-strand break and cross-link repair
  • Non-Homologous End Joining (NHEJ) – DS break repair
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Concerning direct repair:

(a) which organisms can perform this type of repair?
(b) what are the two main methods of direct repair?
(c) outline the major mammalian direct repair pathway.

A

(a) Bacteria and Yeast mainly (can be performed by mammals but this is not common given the simplicity of the repair mechanism)
(b) There are two main methods –

  • Photoreactivation of CPDs – either non-enzymic (200-300nm irradiation) or enzymic (photolyases)
  • Reversal of alkylation damage

(c) There is one mammalian direct pathway – O6-methylguanine-DNA methyltransferase (however it is not commonly used)

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

What is the purpose of base excitions repair (BER)?

Briefly outline the steps involved

A

Removes base damage caused by hydrolysis, ROS etc.

  1. DNA glycosylases identify and remove the damaged base
  2. AP endonuclease and T-phosphodiesterase cut the sugar-phosphate backbone
  3. Gap is filled by DNA polymerase b
  4. Nick is sealed by DNA ligase

NB: There are various BER pathways. The steps for BER are generic (i.e. regardless of the damage) however the glycosylases are specific

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the purpose of nucleotide excision repair (NER)?

Briefly outline the steps involved.

A

Removes damaged nucleotides, particularly CPDs.

  1. Damaged bases are detected
  2. Helicases and nucleases act to open up and cut either side of the mutated base; 24-32bp oligonucleotide is removed
  3. Gap is repaired by DNA polymerase e or d
  4. Nick is sealed by DNA ligase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the purpose of transcription coupled NER? Outline the differences between “normal” NER and transcription coupled NER.

A
  • Transcribed regions are repaired better than untranscribed regions.
  • Preferential repair of transcribed strand (5-10 fold)
  • XPC not required
  • Damaged recognised by stalled RNA pol
  • Additional protein required (not used in global NER) esp CSA and CSB
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Outline the bacterial MMR (mismatch repair) process

A
  1. MutS recognises mismatch
  2. MutL binds MutS and activates MutH
  3. MutH nicks unmethylated (newly replicated) strand
  4. Intervening DNA excised and resynthesised – this repairs correct strand
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Human MMR is similar to bacterial MMR except for the factors - name the human MutS-related and MurL-related factors. Briefly describe their role.

A

MutS-related factors:

  • hMutSa (MSH2 & MSH6) - recognises mismatches and small (1-40bp) loops
  • hMutSb (MSH2 & MSH3) - recognises insertion or deletion loops (IDLs)

MurL-related factors:

  • hMutLa (MLH1 & hPMS2) - major role à interacts with hMutSa and hMutSb
  • hMutLb (MLH1 & hPMS1) & hMutLg (MLH1 & MLH3) - minor roles
17
Q

Name and describe the two major mechnaisms involved in double-strand break repair

A

HR – homologous recombination

  • Requires intact homology template – i.e. sister chromatid
  • Operates during G2
  • Many proteins involved (eg: Rad51, BRCA2)
  • Highly accurate

NHEJ – non-homologous end-joining

  • No homology template required – it just repairs the break in the strands
  • Operates in G1/S/G2
  • Error prone (because it does not have a template)
18
Q

What are the four events in the DNA damage response pathway?

A
  1. Cell cycle checkpoint activation
  2. Transcriptional programme activation
  3. DNA repair
  4. Apoptosis – only occurs if the damage cannot be repaired
19
Q

Concerning checkpoint activation:

(a) what is its purpose?
(b) how is it activated?
(c) name an additional role for transducers.

A

(a) Allows time for DNA repair or apoptosis
(b) Sensors and transducers also activate DNA repair - e.g. NBS/MRE/RAD50 involved in early stages of HR
(c) Transducers also activate DNA repair e.g. phosphoryation of Rad51/52 causes nuclear relocalisation

20
Q

What are the two potential fates of carcinogen DNA?

A

If the DNA can be repaired, you have a healthy cell, if the DNA cannot be repaired, you get apoptosis

21
Q

Concerning RB1 and Rb:

(a) what is RB1
(b) which pathways is it physiologically involved in?
(c) what is Rb?
(d) what is retinoblastoma?

A

(a) RB1 – classic tumour suppressor gene
(b) Involved in G1-G0 transition
(c) mutations in RB1 = Rb (i.e. retinoblastoma)

(d) Malignant cancer of developing retinal cells.
Sporadic disease usually involves one eye. Hereditary cases can be unilateral or bilateral and multifocal.

22
Q

Concerning p53:

(a) what is p53?
(b) how does p53 function (physiologically)?
(c) why is p53 important?
(d) name two common cancers invovled in p53 mutations.

A

(a) p53 – classic tumour suppressor gene
(b) Tumour suppressor gene – Recessive, “two-hit mechanism” - 17p13
(c) Loss or mutation of p53 = most common single genetic change in cancer (> 50% Tumours)
(d) Common cancers involved – breast and colon

23
Q

Concerning ATM:

(a) what is ATM?
(b) what do mutations in ATM cause?
(b) what is AT (ataia telangiectasia)

A

(a) ATM – DNA damage response gene
(b) Mutations = ataia telangiectasia (AT) (autosomal recessive)

(c)

  • Degeneration of cerebellum – ataxia
  • Immune dysfunction
  • Sterility
  • Sensitivity to radiation
  • Increased risk cancer
24
Q

Concerning BRCA1 & BRCA2:

(a) what stage of DNA repair are the BRCA genes involved in?
(b) What % of breast cancers are associated with BRCA mutations?
(c) Name the mutations of BRCA1 and BRCA2
(d) name the cancers that mutations in the BRCA genes are assoited with.

A

(a) Involved in HR (homologous recomination)
(b) Mutations= 5% of breast cancer
(c) BRCA1 = 17q, BRCA2 = 13q
(d) breast, ovarian, prostate, colon (BRCA1), endometiral (BRCA2)

25
Q

Concerning XPA:

(a) what mechanism of DNA repair is XPA involved in?
(b) what do mutations of XPA cause:?
(c) what are the consequences of these mutations?

A

(a) XPA – involved in NER
(b) Mutations = xeroderma pigmentosa (autosomal recessive)
(c) Causes:

  • Sensitivity to UV light
  • Skin cancer
  • Neurodegenration

MCD (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions