DNA REPAIR Flashcards
Xeroderma Pigmentosa (NER gene)
Auto Recessive
Mutations in 9 different NER genes (Locus Heterogeneity.
XP
- EXTREME SUN sensitivity
- Ocular involvement=conjunctivitis, ocular tumors
- 20% have progressive neurologic degeneration
- DNA damage is cumuliative and irrversible
Excision Repair
1) Recognize of Damage
2) Recruit Endonuclease
3) Region excised
4) DNA polymerase fills in Gap
5) Ligase seal nick
Base Excision Repair
Done by DNA glycosylases
- recognizes and removes specific damaged bases in DNA
- e.g Uracil glycosylase.
Mismatch repair
- a type of excision repair shows strand discrimination
- Post replicative repair mechanism
- mismatched bases are recognized and excised
- also inmportant in removing small repeats that tend to expand (e.g triplet expansion disorders)
Tautomerism repair.
Process:
1) mismatch missed by proof reading is recognized by MMR proteins
2) Repair may occur during S-phase (if missed by proof reading) or in G2 when genome is scanned for errors.
3) excision of bases around mismatch
4) Repair by re-synthesis
Hereditary Nonpolyposis Colon Cancer
Results in mutations involving genes encoding mismatch repair proteins
-MSH2, MLH1
Results in microsatellite instability
-microsatellite instability frequently seen with these tuumors=simple repetitive DNA sequences show size variability due to inaccurate replication.
Double Stranded Breaks
Difficult mutation to repair
-dangerous for dividing cells=high probability of loss of genetic material
Two mechanisms of repair:
1) Non-homologous end joining (common)
2) Recombinational repair
- uses homologous chromosome
Ataxia telangiectasia
defect in ATM (11q 22-23)
= A serine threonine kinase wit a number of functions including:
-detecting DNA damege (i.e. sensor) and activating cell cycle arrest and DNA repair proteins (e.g. P53)
Autosomal recessive
- affects cerebellum (=ataxia) and immune system
- increased incidence of cancer
- ocular telangiectasia common
