The unstable genome Flashcards
(26 cards)
What is a nucleotide substitution?
Exchanging one base for another (point mutation rather than frameshift)
What are nucleotide transitions and transversions?
Transitions - pyrimidine substituted for pyrimidine or purine for purine
Transversion - pyrimidine substituted for purine or vice versa
What is a tautomer in genomes?
When hydrogen atoms on bases change position
What can amino groups and keto groups tautomerize into?
Amino groups (-NH2) tautomerize to an imino form (=NH) Keto groups (-C=O) tautomerize to an enol form (=C-OH)
What forms are bases in DNA predominantly in?
Their keto and amino tautomeric forms
What would an adenine tautomer mispairing with a cytosine cause?
An adenine to guanine transition mutation
What happens when base analogues incorporated into DNA?
They can cause mutations eg. a thymine analogue pairs with adenine but the enol tautomer of this thymine analogue pairs with guanine rather than adenine
What is base deamination?
Removal of an amino group from a base
What is the difference between thymine and uracil?
Thymine has a methyl group on carbon 5 whereas uracil only has a hydrogen
Both can base pair with adenine
Why does DNA contain thymine rather than uracil?
- Cytosine can deaminate to produce uracil which base pairs with adenine (rather than guanine)
- Thymine used in DNA so that uracil produced by cytosine deamination can be recognised as base damage and repaired
What causes deamination of bases?
Nitrous acid reacting with bases that contain amino groups
What is adenine deaminated into and what does this cause?
Into hypoxanthine
Causes an adenine to guanine transition
What is depurination of bases?
Hydrolysis of the N-beta-glycosyl bond between the base and pentose sugar
Which does dupurination happen to more - purines or pyrimidines?
Purines (adenine and guanine)
What is the effect of depurination?
Causes apurinic sites that cannot specify the correct base during DNA replication
(Cells may depurinate bases during base excision repair)
What is base akylation?
Transfer of an alkyl molecule such as a methyl group from one molecule to another
Which two bases are most likely to be enzymatically methylated?
Cytosine and adenine
What is the function of methylating DNA in prokaryotes?
Endogenous DNA methylated to distinguish it from exogenous DNA
Under-methylated DNA destroyed by restriction endonucleases
What enzyme methylates adenine residues and what is the function of this process?
DAM methylase (DNA adenine methylation) Helps distinguish parental DNA strand to remove mismatched base errors that occur during DNA replication
In what eukaryotic sequences are cytosine residues most likely to be methylated and what is the function of this?
Cytosine most likely to be methylated in CpG sequences
Promotes formation of Z-form DNA and is involved in repression of gene expression in eukaryotes
What endogenous and exogenous agents can damage DNA?
Endogenous - deamination, reactive oxygen species
Exogenous - ionising radiation, UV light, methylating agents
What are some pathways involved in repairing DNA damage to avoid mutations?
Base excision repair, nucleotide excision repair, mismatch repair, homologous recombination, DNA end joining
What is base excision repair?
Replacing a damaged base with the correct undamaged base
DNA glycosylases remove affected base by cleaving N-glycosidic bond to create apurinic/apyrimidinic site
Site filled in using a DNA polymerase that ultilises the undamaged string as a template
What is nucleotide excision repair?
Two phosphodiester bonds from either side of DNA lesion hydrolysed
Short damaged region removed and gap filled by DNA polymerase which uses undamaged strand as a template
