Flashcards in DNA Repair and Recombination Deck (11):
What can potentially damage DNA integrity
Chemicals - water, uv light, reactive oxygen species etc
What types of spontaneous DNA damage usually occur
Non enzymatic methylation
Methylation of single stranded DNA (ssDNA)
What types of chemical can occur to individual bases
Base oxidation (e.g. guanine oxidation)
Depurination (sugar or nucleotide)
Deamination (NH2 removed)
Name some DNA repair pathways and any major implications in cancer
Base Excision repair (BER)(colorectal cancer)
MissMatch Repair (MMR)(HNPCC)
Nucleotide Excision repair (NER)(skin cancer)
Single Strand Break Repair (SSBR)
DNA Double Strand break repair
DNA interstrand cross link repair
How can we find gene mutations associated with DNA repair
Positional cloning of gene that corresponds to the human disease.
What is the mechanism of Base Excision Repair (BER)
DNA Glycosylases create abasic/aurinic/apyrimidinic (AP) sites (replaces a nucleotide).
Activity signifies damaged bases at the site of insertion.
AP site recognised by AP endonuclease 1. Cleaves the DNA phosphodiester backbone. Polymerases fill the gap. Can either fix the single nucleotide (short patch repair), or fix the whole section (long patch repair)
What happens when Base Excision Repair (BER) doesn't work properly
Causes 'mutator phenotype'
Spontaneous mutations appear far more often
Bad because ^ causes cancer (specifically head/neck/naso-pharyngeal cancer).
What is the mechanism of Single Strand Break Repair (SSBR)
DNA damage recognition.
5' end: APTX (Aprataxin) removes AMP. Polynucleotide 5' kinase adds a phosphate group
3' end: Polynucleotide kinase 3' phosphatase removes the phosphate group. TDP1 (Tyrosyl-DNA-Phosphodiesterase) removes products associated with abortive topoisomerase reactions.
What is the difference between TTRAP and TDP1
They both possess 3' tyrosyl DNA phosphodiesterase activity, but TTRAP also possesses 5' activity
Name a disease associated with Single Strand Break Repair (SSBR) genes
Recessive spinocerebrellar ataxias (uncoordinated movement/gait)