Carcinogenesis

Question 1

Types of DNA damage:

Answer 1

Single-strand breaks 
Double-strand break
mismatch bases
damage base
intra-inter-strand crosslinks

Question 2

Cause of pyrimidine dimers:

Answer 2

UV

Question 3

Causes of single and double strand breaks

Answer 3

Strong radiation

Question 4

Exogenous DNA damaging factors:

Answer 4

UV light
X-rays
Natural isotopes
Chemicals

Question 5

Signature mutation of UV damage

Answer 5

CC to TT.

Bulky lesions

Question 6

Mutation of alkylating agents

Answer 6

GC-AT transition. alkylated guanine can be mismatched with thymine

Question 7

Major surveillance protein which looks for DNA damage =

Answer 7

ATM

Question 8

Deficiency in ataxia-telangiectasia

Answer 8

Human autosomal recessive disorder.

Progressive neurodegeneration, cancer predisposition, premature aging

Question 9

Endogenous p53 mutations usually located at what sites

Answer 9

CpG

Question 10

CpG sites on p53=

Answer 10

Cytosine followed by guainine. Promoter regions that can be silenced when methylated

Question 11

Mechanisms of mutation in CpG sites=

Answer 11

Not methylated cytosine may be spontaneously deaminated to uracil which can be repaired.

If cytosine has been methylated, it may be deaminated to to thymine (not repaired).

GC to AT transmission

Question 12

Repair of alkylation damage:

Answer 12

Direct reversal

Question 13

Molecule involved in direct reversal =

Answer 13

MGMT

Question 14

MGMT

Answer 14

Suicide enzyme. DNA repair enzyme

Question 15

Tumours with reduced MGMT expression are responsive to …

Answer 15

Treatment with alkylating agents

Question 16

Enzymes involved in base excision repair =

Answer 16

DNA glycosylases
Endonuclease
Polymerase
Ligase

Question 17

AP site

Answer 17

No base

Question 18

Nucleoside excision repair is used when

Answer 18

• DNA glycosylases not recognisied

- bulky lesions (e.g. UV)

Question 19

Ex of bulky lesion

Answer 19

UV CC to TT

Question 20

Proteins involved in NER

Answer 20

XP proteins:
Helicase
Endonuclease
Polymerase
Ligase

Question 21

Defect in nucleotide excision repair of UV damage which leads to increased sensitivity to sunlight

Answer 21

Xeroderma Pigmentosum

Question 22

2 repair mechanisms for double strand break:

Answer 22

• Non-homologous end-joining

- Homologous recombination

Question 23

Which kind of repair mechanisms maintains genetic info for double strand break

Answer 23

Homologous recombination

Question 24

Non-homologous end-joining

Answer 24

Clean up ends, ligate back together

Question 25

Homologous recombination =

Answer 25

uses sister chromatid as a template

Question 26

RB1

Answer 26

retinoblastoma

Question 27

BRCA1/BRCA2

Answer 27

hereditary breast and ovarian cancer

Question 28

APC gene is associated with

Answer 28

familial adenomatous polyposis (FAP) colorectal cancer

Question 29

Gene associated with HNPCC

Answer 29

MSH2, MLH1

Question 30

HNPCC

Answer 30

Hereditary non polyposis colorectal cancer

Question 31

Rb sequesters

Answer 31

E2F (transcription factors)

Question 32

BRCA1/2 are =

Answer 32

human genes that produce tumor suppressor proteins

Question 33

2 kinds of hereditary colorectal cancer:

Answer 33

• HNPCC

- FAP

Question 34

Function of APC gene =

Answer 34

Codes for APC protein which sequesters beta catenin to inhibit Wnt target genes

Question 35

Wnt =

Answer 35

Promotes cell proliferation

Question 36

MSH2, MLH1 =

Answer 36

mismatch repair genes

Question 37

Is APC a gatekeeper or caretaker?

Answer 37

Gatekeeper

Question 38

Is MSH1, MLH1 a gatekeeper or caretaker?

Answer 38

Caretaker

Question 39

FAP: problem with gatekeeper or caretaker?

Answer 39

Gatekeeper (APC)

Question 40

HNPCC: problem with gatekeeper or caretaker?

Answer 40

Caretaker

Question 41

‘mutator phenotype’ is found in what kind of cancer?

Answer 41

Hereditary non-polypis colorectal cancer