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BB20023 MCQ 20% EXAM > DNA damage > Flashcards

DNA damage Flashcards

1
Q

Cancer results mainly from?

A

Mutation that arise mainly in DNA damage

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2
Q

DNA damage?

A

modification in the molecular structure of genetic material

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3
Q

Two ways which DNA damage can arise?

A

endogenously: normal metabolism in the cell such as DNA replication and repair
exogenously: environmental sources

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4
Q

DNA damage types

A
  1. Spontaneous DNA damage

2. Environmental DNA damage

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5
Q

DNA repair exists in which organisms?

A

Both pros and eus

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6
Q

Proteins In DNA repair?

A

Highly conserved throughout evolution

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7
Q

Genetic disorder types due to DNA damage

A
  1. Ataxia-telangiectasia (AT)
  2. Degenerative motor condition caused by the failure to repair oxidative damage in the cerebellum
  3. Xeroderma pigmenosum (XP)
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8
Q

XP?

A

a condition characterized by sensitivity to sunlight and linked to a defect in an important ultraviolet UV damage repair pathway

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9
Q

DNA damage repair gene example

A

RAD group

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10
Q

DNA repair processes can be categorised by the functional nature of the repair mechanisms into which three groups

A

Reversal of base damage

excision of base damage

repair of double strand breaks

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11
Q

Function of MTS-alpha

A

recognition of small loops generated by insertions or deletions of NT as well as single base mismatches

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12
Q

MUTS-alpha structure?

A

Hetro-dimer of MSH2 and MSH6

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13
Q

MUTS-beta structure and function?

A

Made up of MSH2 and 3

recognition of small loops during MMR

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14
Q

Subsequent to mismatch recognition, which hetrodimeric complexes are involved?

A

PROTEINS

MLH1 PMS2 AND MLH3

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15
Q

Common cancers caused by MMR?

A

colon, utrine, ovarian, gastric

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16
Q

NT excision repair technique, associated with what type of cancer

A

excision of approximately 30 NT around the damaged site Is used to repair a wide variety of bulky lesions and associated with skin cancer

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17
Q

3 formal stages of NER include?

A
  1. damage recognition
  2. dual incision
  3. Repair synthesis and ligation
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18
Q

What is XPC, function, in what type DNA repair process is it involved in?

A

XPC- A protein called C originally idenitided in patients with zeroderma

stably binds to another protein called HHRAD23

HH- human homologue

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19
Q

reversal of base damage?

Enzyme characteristics

A

Direct repair

DNA damage repaired by which the normal structure is restored.

Single enzyme composed of a single polypeptide chain catalyses a single step reaction

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20
Q

Reversal of base damage involves the/..?

A

breakage and repair of abnormal bonds

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21
Q

Example of reversal of base damage and the enzyme required

A

Photoreactivation (PR) of DNA:

  • Repair of pyrimidine dimers
  • enzyme DNA photolyase (photoreactivating enzyme, deoxyribodipyrimidine photolyases).
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22
Q

Gene encoding DNA photolase in placental mammals

A

gene lost

23
Q

Other enzyme which are involved in direct repair include?

A

6-4 photoproduct lyase, Spore photoproduct lyase, O6-methylguanine DNA methyltransferase

24
Q

Excision of base damage includes?

A

mismatch repair, NT excision repair, Base excision repair

25
Q

excision of base damage mechanisms involve? mediated by

A

a physical removal and replacement of damaged bases mediated by a range of Dif enzyme complexes

26
Q

The enzymatic process is dedicated primarily to the ?

A

Excision fo NT that are incorrectly paired with the (correct) NT on the opposite strand

27
Q

the formation of XPC -HHRAD23 is then followed by?

A

The hetrodimeric complex is then followed by the the recruitment of of other proteins to the site

XPA, RPA, TFIIH AND XPG

28
Q

Which proteins recruited in addition to the XCP-HHRAD23 hetrodimeric complex are involved in the recognition of damaged DNA

A

XPA and RPA

29
Q

Structure and function of TFIIH

A

two subunits with helicase activities;

viz, XPB, XPD that unwind the DNA locally creating a bubble in the DNA

30
Q

Function of ERCC1 and XPF binding the hetrodimeric complex: XPC-HHRAD23

A

generate a complete assembly fo the NE repairosome

31
Q

Describe the process of bimodal incision of DNA and excision of a fragment?- NER

A
  • XPG, a DNA nuclease recruited by RPA/TF11H makes a 3’ incision 3-5 NT from the damaged site
  • The ERCC1-XFP makes a 5’ insision24-25 from the damaged site on the same strand
  • This bimodal incision generates a 27-30 NT fragment which include the damaged base
32
Q

Repair synthesis and ligation process in NER

A

RFC molecular matchmaker loads PCNA trimeric circle onto DNA by dissociating the post incision complex

association with DN pol e and d, resaving with repair synthesis proteins

the gap is filled and repair is ligated

33
Q

Fill in the blanks

BER replaces missing or modified ……….. ………. with its the correct …… …., which is not recognised by the …… ……………. and involves ………….. and ………….. of one ……….. …………

A 
DNA bases 
DNA base 
NER machinery 
excision  and replacement 
single base
34
Q

Most common damage repaired by base excision repair?

A

cytosine deamination to uracil by UV (typically)

35
Q

Base excision repair is initiated by? Process of initiation

A

DNA-repair-specific enzymes- DNA glycosylases

recognises a single or small subset of chemically altered or inappropriate bases

36
Q

Fill In the blanks

an enzyme called ……… ……-……… specifically recognises ……… as an inappropriate base in DNA and catalysis …….. of the …-………….. bond which links the base to the ……..-………… …………….

A 
uracil DNA-glycosylase 
uracil 
hydrolysis
N-glycosidic bond 
sugar-phosphate bond
37
Q

why is excision repair initiated by DNA glycolases called base excision repair

A

bases removed as free bases

38
Q

removal of free bases in base excision repair results in?

A

apurinic or apyrimidinic (AP) sites

39
Q

AP or apurinic site are recognised by and its function

A

enzyme: Ape (apurinic/apyrimidinic) endonucelase

cuts DNA phosphodiester backbone at the 5’ site producing nicks in at this site by hydrolysis

40
Q

deoxyribophosphodiesterases (drpakse)

A

exonuclease that degrade single strand DN and are to inhibited by an imcompletee NT. They are responsible for removing an entire NT

41
Q

The sequential action of DNA glycol’s a 5’ AP endonuclease and the dRpase can generate …

A

a single nucleotide gap in the DNA duplex during base excision repair

42
Q

function of PARP-1

A

poly(ADP-ribose) polymerase-1

assists the repair process by binding to single strand break intermediate and enhances the recruitment of pol b and CRCC1-DNA ligase

43
Q

BER is resolved in a …… ………. or …….. ……….

A

long or short patch

44
Q

In short patch repair?

A

the deoxyribose phosphate is removed and a single NT is inserted at the site of the break

45
Q

In long patch repair?

A

up to 13 NT are inserted and the displaced strand entailing the abasic deoxyribose phos is cleaved by a “flap’ endonulease

46
Q

repair is completed by a

A

ligase

47
Q

repair of double stand breaks by either

A

homologous recombination (HR) or by non-homologous end joining (NHEJ)

48
Q

When does homologous recombination normally occur? involves

A

during meiosis and involves the swapping of large homologs reigns of DNA by recombination

49
Q

damaged sites are repaired by using ?- HR

A

using info on the undamaged homologous region on the chromosome

50
Q

process of HR requires?

A

extensive sequence homology and multiple proteins

51
Q

deficiencies in this repair mech leads to?

A

breast cancer (BRCA1 genes)

52
Q

Non-homologous end joining (NHEJ) involves but does not require?

A

required: mutliprotein complex

not required: homologs regions on the chromosomes

53
Q

one way in which base damage/ strand breaks are allowed to persist in a cell?

A

process of translation DNA synthesis

54
Q

describe the process of translation DNA synthesis (

A
  • replication machinery bypasses sites of base damage
  • allowing DNA replication to proceed down stream of the unrelated damage site,
  • but the use of a ‘sloppy’ polymerases which add NT to the replicating strand opposing the DNA lesion. –> mutations

BB20023 MCQ 20% EXAM (2 decks)

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