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
2 examples of antimetabolites
Methotrexate | 5-FU
26
What do antimetabolites cause?
Double strand breaks - replication associated
27
2 examples of genotoxic natural products
Doxorubicin and bleomycin
28
What do genotoxic natural products cause 2/3
DNA binding/ intercalation | Topoisonerase inhibition
29
3 topoisomerase inhibitors
Irinotecan Comprothecin topo1 Etoposide topi 2
30
What are BRCA1 and 2?
Tumour suppressor genes when mutated lead to hereditary breast cancer
31
What kind of mutations cause TNBRC BRCA?
Germ line LOF mutations
32
What kind of mutations can we find in brca in sporadic triple negative breast cancer?
Deleterious
33
What do BRCA genes do?
Repair DS breaks by HRR AND FA
34
What is PARP1?
Component of nucleotide excision repair involved in removal of base adducts
35
What does inhibition of PARP1 do?
Prevents repair base modification using bulky adducts
36
Current BRCA cancer approved drugs 2
Olaparib | rucaparib a
37
How is Rb involved in DNA repair?
NHEJ
38
What does Rb do?
Tumour suppressor gene executing G1 checkpoint control
39
4 cancers with somatic deleterious Rb
Sarcoma Glioblastoma SCLC HR prostate