Genetics of cancer

Question 1

Does cancer cell resist apoptotic signals?

Answer 1

Yes

Question 2

What are some causes of damage to cell genomes/DNA

Answer 2

• Errors during DNA replication
• Constant attack from endogenous biochemical processes inside the cell
• Occasional attack from exogenous mutagens (environment) and their metabolites

Question 3

What is a function of the MMR mechanism? (Mismatch repair)

Answer 3

They monitor recently synthesized DNA in order to detect miscopied DNA sequences that have been overlooked by the proofreading

Question 4

What can happen due to endogenous biochemical processes?

Answer 4

• Depurination
• Depyrimidation
• Base deamination

Question 5

What are some examples of Exogenous mutagens?

Answer 5

• UV radiation
• ROS (can also be endogenous if ROS is from mitochondria)
• Chemical carcinogens
  Chemical carinogens can be divide into:
• Base-modifying agents (alkylating agents)
• DNA aducts
• Base analogues (they replace bases)

Question 6

Explain BER

Answer 6

Repair of lesion in the DNA that derive from ENDOGENOUS sources

The enzyme involved: DNA glycosylase. It will identify the modified base and removes it out of the double helix together with a few downstream bases. The empty spaces what’s left now is called AP (Apurinic-/ Apyrimidic site –>Abasic). AP endonuclease cleaves this region to yield free OH3’–5’P. DNA Poly I identifies the free space and adds the correst bases in 5–>3 prime direction. The only small left space needs to be ligased with DNA ligase

Question 7

Explain NER

Answer 7

Repair lesions created by EXOGENOUS sources such as UV

NERis accomplished by enzymes that recognize bulky, helix distortion lesion and cleave the flanking Oligonucleotide sequences at sites +- 24 nucleotides on the 5’ side and about 5 nucleotides on the 3’ side. The resulting +- 29 nucleotide ss gap in the DNA is then filled by DNA poly o or e, acting together with PCNA and RPA and is finally sealed by DNA ligase

Question 8

What 2 sub detection pathway exists in NER?

Answer 8

• Global genomic NER (GG-NER) –> removes damage anywhere in the genome
• Transcription coupled NER (TC-NER) –> specifically repairs transcription-blocking lesion in actively transcribed DNA

Question 9

When is HR mechanism induced?

Answer 9

During late S phase and G2 phase of the cell cycle. It uses the sequence in the undamaged sister chromatid (Homology)

Question 10

When is NHEJ is induced?

Answer 10

When there is no sequence of a sister chromatid is available