DNA Damage and Repairs

Question 1

4 endogenous sources of DNA damage

Answer 1

1. Replication errors
   - DNA pol may incorporate incorrect nucleotide or slip out of proper alignment.
2. Double strand breaks in DNA can occur when the cell is passing through S phase. More susceptible to breaks while it is unraveling.
3. Spontaneous damage due to deprurination (~10,000 per day) or depyrimidination (less frequent)
4. Free radial formation can lead to damage of bases and single or double strand breaks in DNA

Question 2

Is depurination or depyrimidination more common? This is an example of which type of DNA damage?

Answer 2

Depurination is more common. Happens about ~10,000 per day.

Spontaneous damage, which is an example of endogenous DNA damage.

Question 3

What natural processes causes free radicals?

Answer 3

Normal metabolic processes such as the ETC and immune responses can generate free radicals.

Question 4

The most concerning type of free radical

Answer 4

Are those derived from oxygen. Free radicals derived from oxygen are collectively known as ROS (reactive oxygen species)

Question 5

Free radicals derived from oxygen are collectively known as?

What are examples of free radicals formed from oxygen?

Answer 5

Reactive oxygen species.

Ex: Superoxide, peroxide, hydroxyl radical. These all have unpaired electrons.

Question 6

Free radicals can cause damage to molecules by stealing their electrons through

Answer 6

Oxidation

Question 7

What controls oxidative damage by neutralizing free radicals?

Answer 7

Antioxidants.

Question 8

Enzyme and non-enzyme Antioxidants

Answer 8

Enzyme- superoxide dismutase, catalase, and glutathione peroxidase

Non-Enzyme- Vitamin C (ascorbic acid), Vitamin E, Copper, selenium, Zinc, and glutathione.

Question 9

Exogenous sources of DNA damage

Answer 9

1. Non-ionizing radiation (UV light from the sun)
2. Ionizing radiation (X-rays, CT scans)
3. Chemicals (air pollutants or pesticides)

Question 10

How can non-iodizing radiation cause DNA damage

Answer 10

radiation from the sun.

Causes covalent bonds that crosslink adjacent bases (almost always happens to pyrminidines)
-Leads to distortion of DNA that blocks transcription and replication.

Generates free radicals within cells
-Can lead to damage of

Question 11

How can iodizing radiation cause DNA damage

Answer 11

Radiation from CT scan or X ray

Generates free radicals within the cells.

Question 12

How can chemicals cause

Answer 12

Ex: air pollutants or pesticides.

Form DNA adducts- segment of DNA attached to a molecule like an alkyl group (groups are bulky and can block transcription and replication)

Also generates free radicals

Question 13

Gene expression is the process of

Answer 13

Transcription and translation

Question 14

6 ways to repair DNA

Answer 14

1. Proofreading by DNA polymerase
2 Mismatch repair 
3. Base excision repair 
4. Nucleotide excision repair
5. DNA double-strand break repair: homologous recombination or non-homologous end joining. 
6 Direct reversal

Question 15

What occurs during mismatch repair?

Answer 15

Goal is to repair the mismatched bases that escaped proofreading by DNA pol.

• Enzymes methylate the parent strand where the complementary daughter strand is incorrect.
• Endonuclease cleaves the daughter strand on each side of the incorrect base (nicking)
• Exonuclease removes the incorrect base (digestion)
• DNA pol fills in gaps and DNA ligase seals (resynthesis and ligation)

Question 16

What occurs during base excision repair

Answer 16

Repairs a single damaged base.

Glycosylases are a family of enzymes that recognize and remove a single damaged base and leaves an basic site in one strand of the NDA.

• Endonucleases cleaves the sugar phosphate backbone
• Exonuclease removes
• DNA pol fills in the gap and DNA ligase seals

Question 17

What occurs during nucleotide excision repair (NER)

Answer 17

Repairs multiple damaged bases.

• A protein complex recognizes the damaged bases and causes a denaturation bubble to form around the damage.
• Endonucleases cleave the strand on either side of the damage.
• Exonucleases removes
• DNA pol fills it in and DNA ligase seals it

Question 18

What occurs during the DNA double stranded break repair

Answer 18

1. Homologous recombination (HR)
   - Involves replication and uses a similar or identical molecule of dsDNA as the template.
2. Non-homologous end-joining (NHEJ)
   - rejoining of broken ends without replication

Question 19

What occurs during direct reversal

Answer 19

Repairs damage that occurs due to the addition of chemical groups. Enzymes remove the chemical groups that were added.

Question 20

If the damage to DNA cannot be repaired, there are 3 possible responses by the cell. They are:

Answer 20

1. The cell may become senescent and enter G0
2. The cell may become apoptotic
3. The cell may become malignant and develop immortal characteristics.