L17 DNA Damage And Repair Flashcards
What is the need for DNA repair
Errors can occur despite proof reading
DNA is constantly being subjected to environmental stress which can cause addition or removal of bases
What are the causes of DNA damage
Can be chemicals(ex: nitrous acid which can delaminate bases)
Radiation(ex: uv rays can cause fusion of 2 pyrimidines)
Bases can also be altered or lost spontaneously
What is mismatch repair
Corrects mismatched bases by Mut proteins
Occurs within minutes of replication
Reduces error rate from 1 in 107 to 1 in 109 nucleotides
Steps of mismatch repair
Mut proteins identify mispaired nucleotides
According to degree of methylation
(Methylated=correct)
Endonuclease nicks strand and bases are removed by exonuclease
Gap is filled by DNA polymerase and new strand by DNA ligase
What is nucleotide excision repair
Due to exposure of UV rays
Covalent joining of 2 adjacent pyrimidines and produce a dimer
What are steps of NER
Uv specific endonuclease(uvrABC exinuclease) recognizes dimer and cleaves damaged strand
Gap is filled using DNA poly 1 and DNA ligase
NER occurs throughout cell cycle
What is base excision repair
DNA bases can be altered (cytosine slowly deaminates to form uracil)
Or bases can be lost Spontaneously
Corrected by BER
What are the steps of BER
Abnormal bases are recognized by DNA glycosylases that hydrolytically cleave them from the deoxyribosephosphate
Leaving an AP site
Specific AP endonuclease initiates process of excision and gap filling
DNA pol1 and DNA ligase complete repair process
What is double strand break repair
Due to ionizing radiation double strand breaks in DNA occur
Either nonhomologus end joining or homologous recombination
Disease due to mismatch repair
Associated with nonpolyposis colorectal cancer
Disease due to NER
Xeroderma pigmentosem
Extensive accumulation of mutation
Disease due to DSB
BRCA1 or BRACA2 breast and ovarian cancer
Fanconi anemia due to dec ability to repair interstrand DNA cross links
Anemia and mental retardation
Types of repair systems
Mismatch repair
Base excision repair
Nucleotide excision repair
Double strand break repair
