L6: DNA repair Flashcards
What are the causes of DNA damage?
Exogenous
❖ Physical agents: X-ray, U.V.R.s
❖ Chemical agents: as Nitrous acid
Endogenous
❖ Spontaneous
❖ During replication
What are the types of DNA damage?
1) Alteration or removal of one base
2) Alteration or removal of two bases or more e.g. thymine dimer which causes a kink or distortion in DNA helix.
What happens if the damage wasn’t repaired?
If the damage is not repaired, a permanent mutation occurs which may result in a hereditary disorder
What are the main steps for DNA repair?
Recognition of the lesion: This is the function of an endonuclease, which cleaves the damaged strand to form a cut (nick).
Excision of damaged DNA: The damaged part is removed by exonuclease.
Filling of the gap with the correct nucleotide: This is catalyzed by a DNA polymerase beta.
Ligation: This is catalyzed by DNA ligase
What are the mechanisms of DNA repair?
❖ The most common mechanisms of DNA repair are:
1) Mismatch repair (replicative errors).
2) Excision repair (correct the effect of exogenous agents): this mechanism includes:
Base excision repair (BER).
Nucleotide excision repair (NER).
Mismatch repair(replicative errors)
❖ It corrects errors occurring during DNA replication.
❖ During replication, specific enzymes(DNA nuclease complex) scan the newly synthesized strand.
❖ Three enzymes are involved in this mechanism:
1) If a mismatch is detected, it is Cut by nuclease
2) Gap is filled by DNA polymerase beta
3) DNA ligase Seals the break
Excision repair
❖ The most common type of repair
❖ It corrects DNA damage caused by exogenous agents either chemical or physical.
❖ It includes:
Base excision repair (BER)
Nucleotide excision repair (NER)
What are the diseases related to defects in DNA repair?
❖ Diseases related to defect in Mismatch Repair:
Hereditary Non-Polyposis Colon Cancer (HNPCC)
❖ Diseases Related to defect in Nucleotide Excision Repair:
xeroderma pigmentosum (XP)
some cancers
neurodegenerative diseases
What is the nature of Xeroderma pigmentosum (XP)?
It is a rare autosomal recessive disease.
Compare between base excision repair and nucleotide excision repair
What causes xeroderma pigmentosum?
It is due to absence of UV-specific endonulease enzyme and defective correction of thymine dimmer (Nucleotide excision repair defect).
What characterizes xeroderma pigmentosum?
It is characterized by marked sensitivity to sun light (ultraviolet) with subsequent development of:
- skin damage
- multiple skin cancers
- premature death
