Exploiting DNA damage Response Flashcards

1
Q

6 types of DNA damage

A
Single strand break
Double strand break
Vase modification 
Base cross links/addicts
A basic sites
Base mismatch
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2
Q

What damage does replication stress cause?

A

Double strand break

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3
Q

What damage does ionising radiation cause?

A

Single strand break
Ds break
Base modification

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4
Q

What damages does metabolism cause

A

Ds break
Base modification.
Base cross links/adducts

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5
Q

What damage does UV light cause?

A

Base cross links and adducts

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6
Q

What damage do abasic sites cause

A

Single strand break

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7
Q

What caused base mismatch

A

DNA replication error

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8
Q

What are abasic sites caused by

A

Instrinsif molecular instability

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9
Q

What do cells do when they experience DNA damage?

A

Initiate DDR

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10
Q

What is DDR?

A

A network of cellular pathways that sense, signal and repair the DNA lesion

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11
Q

7 types of DNA Damage repair

A
Base excision repair
Non homologous end joining
Homologous recombination
Nucleotide excision repair
Franconi Anemia
Direct reversal
Mismatch repair
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12
Q

What does base excision repair work on?

A

Ss breaks
Abasic sites
Base oxidation/ alkylation

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13
Q

NHEJ is used in

A

Double strand breaks

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14
Q

HRR is used in

A

Double strand break

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15
Q

Nucleotide excision repair is used in

A

Single strand break
Base oxidation/ alkylation
Base cross link adducts

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16
Q

FA is used in

A

Base cross links/adducts

17
Q

Direct reversal is used in

A

Base oxidation/ alkylation

18
Q

Mismatch repair fixes

A

Base mismatch

19
Q

What is therapeutic index

A

Differential in dose of a therapeutic agent that causes the therapeutic response to the amount that caused unmanageable adverse effects

20
Q

What is therapeutic window

A

Range of doses that produces response without causing any significant adverse effect in patients

21
Q

3 examples of alkalyting agents

A

Cyclophosphamide
Do I
Temozolomid

22
Q

What do alkalyting agents cause

A

Simple and complex base adducts

23
Q

2 examples of platinum salts

A

Cisplatin

Carboplatin

24
Q

What do platinum agents caused

A

Complex base adducts

25
Q

2 examples of antimetabolites

A

Methotrexate

5-FU

26
Q

What do antimetabolites cause?

A

Double strand breaks - replication associated

27
Q

2 examples of genotoxic natural products

A

Doxorubicin and bleomycin

28
Q

What do genotoxic natural products cause 2/3

A

DNA binding/ intercalation

Topoisonerase inhibition

29
Q

3 topoisomerase inhibitors

A

Irinotecan
Comprothecin topo1
Etoposide topi 2

30
Q

What are BRCA1 and 2?

A

Tumour suppressor genes when mutated lead to hereditary breast cancer

31
Q

What kind of mutations cause TNBRC BRCA?

A

Germ line LOF mutations

32
Q

What kind of mutations can we find in brca in sporadic triple negative breast cancer?

A

Deleterious

33
Q

What do BRCA genes do?

A

Repair DS breaks by HRR AND FA

34
Q

What is PARP1?

A

Component of nucleotide excision repair involved in removal of base adducts

35
Q

What does inhibition of PARP1 do?

A

Prevents repair base modification using bulky adducts

36
Q

Current BRCA cancer approved drugs 2

A

Olaparib

rucaparib a

37
Q

How is Rb involved in DNA repair?

A

NHEJ

38
Q

What does Rb do?

A

Tumour suppressor gene executing G1 checkpoint control

39
Q

4 cancers with somatic deleterious Rb

A

Sarcoma
Glioblastoma
SCLC
HR prostate