Mutations Flashcards
What molecules proof read DNA
DNA polymerase
What environmental factors cause mutations?
UV - pyrimadines bond to one another
ionising radiation
chemical agents - point mutation, insertion/deletion
Cause of point mutations
nitrous acid oxidatively deaminates aromatic primary amines
nitrate
alkylating agents - transversions
Cause of insertion/deletion
intercalating agents wedge between bases, distorting DNA helix
Effects of mutation
change in DNA = change in RNA
frameshift mutations
polar mutation - affects downstream genes/operons
hydrophobic/hydrophilic AAs formed
chromosomal changes: segmental duplications - recombination, deletion of DNA between duplicates; whole chromosomal duplication
Carcinogenic mutations
point mutations can irreversibly alter cellular metabolism, can cause cancer when DNA affected or its repair/replication
Tests for carcinogens
Ames test - bacteria that cannot make histidine
Liver enzymes - only carcin. when enzymes try to detoxify
DNA repair methods
- direct reversal
- base excision repair
- nucleotide excision repair
- mismatch repair
Direct reversal
pyramidine dimers via photoreactivation revert to single entities (not in humans)
alkyltransferases reverse base methylation caused by alkylating agents
Base excision repair
remove and repair
glycosylases cleave glycosidic bond of corresponding altered nucleotide (on 5’ side by AP endonuclease)
NTs removed by deoxyribose phosphate lyase
gaps filled by DNA polymerase and ligase
Nucleotide excision repair
corrects pyrimidine dimers and other lesions causing displacement of bases
NER responds to helix distortions
repair UV and smoke damage
Mismatch repair
- nonhomologous end-joining: directly joins double-stranded breaks, protein Ku is broken down DNA sensor
- homologous end-joining: recombination via 2 Holiday junctions, DNA polymerase fills gaps and ligase seals
