DNA repair system lecture

Question 1

a group of mechanisms, by which a cell identifies and corrects damage of the DNA molecules is?

Answer 1

DNA repair

Question 2

DNA damage sources can be subdivided into two main sources:

Answer 2

– Endogenous damage

– Exogenous damage

Question 3

Exogenous damage?

Answer 3

• Ultraviolet radiation
• Radiation: X-rays, gamma radiation
• Chemicals
• Pollution
• Smoking

Question 4

Endogenous damage?

Answer 4

1. Normally the metabolic processes inside the cells produce highly reactive
   oxidizing particles called Reactive Oxygen Species (ROSs)
2. Replication errors

Question 5

what are Reactive Oxygen Species?

Answer 5

Those ROSs are highly injurious to many cellular components including the DNA

Question 6

when a cell exposed to dna damage, diff. repair mechanism are activated to relieve this damage > if they fail to repair apoptosis pathway is activated > if it is malignant transformation may occur

Answer 6

…

Question 7

what is apoptosis?

Answer 7

a form of programmed cell death that occurs in multicellular organisms

Question 8

what is malignant transformation?

Answer 8

is the process by which cells acquire the properties of cancer

Question 9

Types of DNA damage?

Answer 9

1. Base loss
2. Chemical modification of the base
3. Thymine dimer
4. Single and double strand breaks

Question 10

1. Base loss?

Answer 10

– Within a typical mammalian cell, several thousand purines and pyrimidines are spontaneously lost per day.
– Loss of a purine or pyrimidine base creates an
apurinic/apyrimidinic (AP) site

Question 11

2. Chemical modification of the

base?

Answer 11

– For example deamination of the bases.

• Some Chemicals e.g. nitric oxide promote deamination of nitrogenous base

– Nitric oxide is a pollutant produced mainly in areas of high motor vehicle traffic, such as in large cities.

Question 12

3. Thymine dimer?

Answer 12

– Exposure of a cell to ultraviolet rays can result in covalent linking of adjacent thymine residues

– This distorts the DNA so that these two bases no
longer pair with their adenine partners.

Question 13

4. Single and double strand breaks?

Answer 13

• Single-strand and double-strand breaks are produced at low frequency during normal DNA metabolism.

– Breaks are also produced by ionizing radiation, ultraviolet rays and gamma radiation.

Question 14

DNA repair systems?

Answer 14

1. Nucleotide excision repair
2. Base excision repair
3. Mismatch repair
4. Repair of double strand breaks

Question 15

Nucleotide excision repair recognizes

bulky damages such as?

Answer 15

thymine dimmers that occur due to ultraviolet (UV) light

Question 16

The process needs cooperative function of a group of enzymes and proteins:

Answer 16

1. Uvr-ABC excinuclease: it is a specific endonuclease that recognizes the dimmer and cleaves the damaged
   strand on both sides of the dimmer
2. A short oligonucleotide containing the dimmer is
   excised, leaving a gap which is filled by DNA polymerase
3. The nick is sealed by ligase enzyme

Question 17

what does Base excision repair do?

Answer 17

repairs damage to a single nucleotide

Question 18

There are 5 enzymes used in Base excision repair which are?

Answer 18

1. DNA glycosylase: removes the abnormal base by cleaving the
   glycosidic link to create an AP site
2. AP endonuclease: cuts the internal
   phosphodiester bond
3. AP lyase: removes the remaining sugar
   phosphate residue.
4. DNA polymarase : fills the gap
5. DNA ligase : Seals the nick

Question 19

2 Examples of defective DNA repair systems?

Answer 19

1- Hereditary nonpolyposis colorectal cancer (HNPCC): high risk of colon cancer, caused by mutation in the proteins involved in mismatch repair
sys

2- Xeroderma Pigmentosum: caused by impairment of nucleotide excision repair system (Uvr ABC) required for repair of thymine dimmers, characterized by the formation of multiple skin lesions and cancer on exposure to sunlight

3- Ataxia-telangiectasia (AT): rare neurodegenerative disorder characterized by ataxia, telangiectasia, immunodeficiency. caused by impaired double-strand break repair system