Forensic Biology - DNA Damage and Repair
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- Created by: aarafa11
- Created on: 29-05-20 21:10
How does Single nucleotide polymorphism cause sickle cell anaemia
changes Glutamine (uncharged polar amino acid residue) to Valine (non-polar amino acid residue); low O2, when Hb changes conformation- Valine residue allows hydrophobic interactions to occur between Hb proteins. will form a fibrous percipitate
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*** doe Single nucleotide polymorphism cause a stop codon
Ribosome stops translation early because the mutation has changed a codon for an amino acid for a stop translating codon; Result – short, non-functional protei
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How can there be errors in replication
nucleotide with the wrong base; geometry of h-bond; frayed DNA end from the DNA polymerase 2nd active site acts as a exonucleas; Conformational change in the DNA polymerase
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how id DNA damaged
Ionizing radiation; UV radiation; Heat; Chemicals (including some produced by the cells own metabolism)
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what does ionizing radiation do to DNA
breaks the sugar-phosphate backbone
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what does UV radiation do to DNA
radiation-causes pyrimidine bases (C & T) to react, forming a dimer
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what does Heat – depurination do to DNA
spontaneous hydrolysis splits A & G from the sugar-phosphate backbone)
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why is depurination the most common reason of DNA damage
DNA in each human cell looses about 18,000 purine bases a day, due to body temp.
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what are the chemical damage principle forms
direct bind to DNA; direct reaction with base (altering pairing abilities); de-amination
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what does chemical modification do to DNA
Disrupts base pair bonding, causing bulky lesions – distortion of the DNA molecule
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How is direct reaction - oxidative damage formed
free radicals (O2-* & HO*) & H2O2;
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What is the consequence of oxidative damage
DNA strand breakage and misreading; altered gene expression; chromosomal instability; Cytostasis; and neoplastic growth
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How is methylation damage formed
Caused by uncontrolled methylation by the methyl group donor S-adenosyl-methionine (SAM)
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How is deamination caused in DNA
Caused by spontaneous hydrolysis; Oxygen from water incorporated into Cytosine; Followed by structural shift to form Uracil
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What are the possible ways to repair DNA
Nucleotide Excision Repair (NER); Base Excision Repair (BER); Mismatch Repair; Double-strand Breakage Repair
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What 2 pathways does Nucleotide Excision Repair (NER) to repair DNA
Transcription-coupled pathway; Global pathway
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What is Nucleotide Excision Repair (NER) 'cut & patch' mechanism
Active against bulky lesions by pyrimidine dimer or nucleotides that have reacted with other chemicals
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Which enzyme is used Base Excision Repair (BER)
Repair initiated by DNA Glycosylase which remove the altered base from the sugar
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How does Base Excision Repair (BER) work
De-amination leads to Uracil replacing cytosine; DNA glycosylase recognises the change so removes the base from sugar
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What initiates repair for depurination and Base Excision Repair BER (after DNA glycosynase beheading)
Enzyme AP endonuclease cleaves the sugar phosphate backbone; DNA Polymerase β removes the sugar-phosphate remnant & inserts a nucleotide complementary to the undamaged strand; DNA ligase III seals backbone
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Why proof read the mismatched repair need to be done
5-methyl Cytosine can be de-aminated to T - a transition mutation
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How would cells know which base in the pair is wrong in a new synthesised DNA
Nicks (Single-strand break) are present in the newly synthesised strand; MutS protein recognises mis-match; 2nd protein MutL scans for nick on the newly synthesised strand; New strand digest by activated MutS complex
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What causes Double strand breakage (DSB)
by ionising radiation, stalled replication, reactive oxygen species
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What happen if Double strand breakage (DSB) repair isn't done
Chromosomes abnormalities
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WHat is the most common pathway for Double strand breakage (DSB) in mammals
Non-homologous end joining (NHEJ)
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Which repair mechanism is used when 1 of the strand of a DNA breaks
Base Excision Repair (BER)
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What happens when repair machinery fails
mutation in DNA; senescence; apoptosis; cancer
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Other cards in this set
Card 2
Front
*** doe Single nucleotide polymorphism cause a stop codon
Back
Ribosome stops translation early because the mutation has changed a codon for an amino acid for a stop translating codon; Result – short, non-functional protei
Card 3
Front
How can there be errors in replication
Back
Card 4
Front
how id DNA damaged
Back
Card 5
Front
what does ionizing radiation do to DNA
Back
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