Induced Mutations & Repair Flashcards
True or false: Sickle cell is a Recessive mutation (recessive gene)
True
True or false: Malaria resistance is a dominant trait in sickle cell
Yes, so you can be a carrier of sickle cell but can actively have resistance to malaria
What mutation in the codon happens to code for sickle cell haemoglobins
Point and Mis-sense: CTT changes to CAT causing changes in transcription and coding
What is the cause of spontaneous mutation
DNA polymerase proof reading errors (Rare)
What are vase analogues in terms of chemical mutagens
“Normal” based but with mods making them tautomerise leading to mispairing.
What is a substrate transition
When a base changes to another base causing the transcribed substrate to be changed. This happens during incorporation NOT LATER
What do deaminating and ally laying agents do to DNA bases in situ
Modify side groups of bases e.g. by nitrous acid
- cytosine to Uracil
- adenine to hypo-xanthine
- 5-methylcytosine to thymine
Why are 5-methylcytosine bases a hotspot for deamination mutations
Foreign bases trigger DNA dense mechanisms but the mutation of 5-methylcytosine to Thymine IS NOT RECOGNISED because Thymine isn’t a foreign base.
What’s does base alkylation do
Modified sites on both pyrimidines and purines especially Guanine
- Leads to both transversions and transitions
Describe the affect of frameshift mutagen Acridine
Dirivitaves (From cigarettes) lead to insertion of base. These bases intercalate between base pairs causing a disruption of polymerase
Why are runs of repeated bases hot spots for frameshift mutations
Easier for one base to be added or deleted in a long run of the same base e.g. AAAAA
What are the two ways a mutation can be induced
Chemical mutagen or Ionising radiations
Give examples of the most common environmental (radiative) mutagens
UV light Cosmic rays (gamma) Radon (alpha particles)
Describe characteristics of UV radiation
Specific effects used in labs to induce mutation. Most effective at 260nm = max ab. For DNA. Causes adjacent Ts to dimerise leading to helix distortion and rep mechs aren’t always 100%
Describe how the Deoxydipyrimidine photolyase DNA rep mech works
IV dimerised thymine, light dependant UV, cleaves T dimers —> error free
- pyrimidine only
How does DNA methyl transferase rep mech work
Reverse action of alkylation by transferring methyl/ethyl groups from guanine and Thymine to an internal Cysteine residue on the enzyme
Describe how the Glycosylate DNA reps mech works
Removes alkylated or foreign bases by cleaving nucleoside bonds between deoxyribose sugar and base
- leave Apurinic or Apyrimidinic site (AP site) Whig is repaired by general rep mech
Name 3 types of specific DNA repair mechanism
Deoxydipyrimidine Photolyase
DNA Methyl Transferase
Glycosylate
Name some general repair mechanisms
Proofreading ability of DNA p
SOS response
Suppression
Inherent resistance
Describe the DNA polymerase proofreading ability
Has a 3’-5’ exonuclease activity as well as 5’-3’ extension activity.
Detects and responds to base mismatches/irregularities caused by dimers or DNA binding molecules
What are 3 steps of DNA Polymerase proofreading
Endonuclease Cleavage
DNA gap filling
Ligation
Describe the Exonuclease cleavage step of DNA Polymerase proofreading
Enzymes involved are specific to 5’ or 3’ end of lesion.
Dimers removed through excision by specific complex’s
Mismatches removed through cleaving at GATC sites by specific complexes
Describe the second step of DNA Polymerase proofreading
DNA gap filling. Polymerase uses free 3’-OH group in the gap to add sequential bases using intact strand as template.
Describe the final step pf DNA polymerase proof reading
DNA ligation. 3’-OH Of new patch ligated to 5’-Phosphate terminus of original strand to give one DNA molecule
