DNA repair system lecture Flashcards
(19 cards)
a group of mechanisms, by which a cell identifies and corrects damage of the DNA molecules is?
DNA repair
DNA damage sources can be subdivided into two main sources:
– Endogenous damage
– Exogenous damage
Exogenous damage?
- Ultraviolet radiation
- Radiation: X-rays, gamma radiation
- Chemicals
- Pollution
- Smoking
Endogenous damage?
- Normally the metabolic processes inside the cells produce highly reactive
oxidizing particles called Reactive Oxygen Species (ROSs) - Replication errors
what are Reactive Oxygen Species?
Those ROSs are highly injurious to many cellular components including the DNA
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
…
what is apoptosis?
a form of programmed cell death that occurs in multicellular organisms
what is malignant transformation?
is the process by which cells acquire the properties of cancer
Types of DNA damage?
- Base loss
- Chemical modification of the base
- Thymine dimer
- Single and double strand breaks
- Base loss?
– 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
- Chemical modification of the
base?
– 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.
- Thymine dimer?
– 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.
- Single and double strand breaks?
- 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.
DNA repair systems?
- Nucleotide excision repair
- Base excision repair
- Mismatch repair
- Repair of double strand breaks
Nucleotide excision repair recognizes
bulky damages such as?
thymine dimmers that occur due to ultraviolet (UV) light
The process needs cooperative function of a group of enzymes and proteins:
- Uvr-ABC excinuclease: it is a specific endonuclease that recognizes the dimmer and cleaves the damaged
strand on both sides of the dimmer - A short oligonucleotide containing the dimmer is
excised, leaving a gap which is filled by DNA polymerase - The nick is sealed by ligase enzyme
what does Base excision repair do?
repairs damage to a single nucleotide
There are 5 enzymes used in Base excision repair which are?
- DNA glycosylase: removes the abnormal base by cleaving the
glycosidic link to create an AP site - AP endonuclease: cuts the internal
phosphodiester bond - AP lyase: removes the remaining sugar
phosphate residue. - DNA polymarase : fills the gap
- DNA ligase : Seals the nick
2 Examples of defective DNA repair systems?
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
