Lecture 04 Flashcards
Base Excision Repair
DNA glycosylase “flips out” bases from helix, scanning for damage and cleaves glycosyl bond connecting incorrect base with sugar.
Nucleotide Excision Repair
Multienzyme complex scans DNA for global distortions and cleaves phosphodiester bonds on either side of distortion. DNA helicase peels away lesion-containing strand
Transcription-coupled Repair
RNA polymerase stalls at lesions and directs repair machinery. Strand specific.
Cockayne’s Syndrome
Defect in transcription-coupled repair; RNA polymerase is permanently stalled at damage sites in important genes
Methylated cytosines
Deamination of methyl-C produces T mismatched with G; DNA glycosylase repairs error, but it is relatively ineffective - accounts for 1/3 of all point mutations
Translesion polymerases
Useful for cases of extensive damage to the cell; less accurate back up polymerases repair damage - but no proofreading ability
Double-strand Break Repair
Non-homologous end joining brings broken strands together, rejoined by DNA ligation - but one or more nucleotides will be lost
What are 3 DNA damage checkpoints in the cell?
If DNA damage is triggered:
- Entry from G1-S phase is blocked
- Progression through S phase is slowed
- Transition from G2-M phase is blocked
ATM Protein
Kinase that generates intracellular signals which alert cell to DNA damage and upregulate expression of DNA repair genes; mutations lead to ataxia telengiectasia
Homologous recombination
Genetic exchange between a pair of homologous DNA sequences which repairs double strand breaks and exchanges genetic information via crossover
Hybridization/renaturation
DNA double helix reforms from its separated single strands
Heteroduplex DNA
Double helix created from strands that originate from different molecules
Loss of heterozygosity
Non-functioning homolog used to “repair” other homolog
