Induced Mutations & Repair

Question 1

True or false: Sickle cell is a Recessive mutation (recessive gene)

Answer 1

True

Question 2

True or false: Malaria resistance is a dominant trait in sickle cell

Answer 2

Yes, so you can be a carrier of sickle cell but can actively have resistance to malaria

Question 3

What mutation in the codon happens to code for sickle cell haemoglobins

Answer 3

Point and Mis-sense: CTT changes to CAT causing changes in transcription and coding

Question 4

What is the cause of spontaneous mutation

Answer 4

DNA polymerase proof reading errors (Rare)

Question 5

What are vase analogues in terms of chemical mutagens

Answer 5

“Normal” based but with mods making them tautomerise leading to mispairing.

Question 6

What is a substrate transition

Answer 6

When a base changes to another base causing the transcribed substrate to be changed. This happens during incorporation NOT LATER

Question 7

What do deaminating and ally laying agents do to DNA bases in situ

Answer 7

Modify side groups of bases e.g. by nitrous acid

• cytosine to Uracil
• adenine to hypo-xanthine
• 5-methylcytosine to thymine

Question 8

Why are 5-methylcytosine bases a hotspot for deamination mutations

Answer 8

Foreign bases trigger DNA dense mechanisms but the mutation of 5-methylcytosine to Thymine IS NOT RECOGNISED because Thymine isn’t a foreign base.

Question 9

What’s does base alkylation do

Answer 9

Modified sites on both pyrimidines and purines especially Guanine
- Leads to both transversions and transitions

Question 10

Describe the affect of frameshift mutagen Acridine

Answer 10

Dirivitaves (From cigarettes) lead to insertion of base. These bases intercalate between base pairs causing a disruption of polymerase

Question 11

Why are runs of repeated bases hot spots for frameshift mutations

Answer 11

Easier for one base to be added or deleted in a long run of the same base e.g. AAAAA

Question 12

What are the two ways a mutation can be induced

Answer 12

Chemical mutagen or Ionising radiations

Question 13

Give examples of the most common environmental (radiative) mutagens

Answer 13

UV light
Cosmic rays (gamma)
Radon (alpha particles)

Question 14

Describe characteristics of UV radiation

Answer 14

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%

Question 15

Describe how the Deoxydipyrimidine photolyase DNA rep mech works

Answer 15

IV dimerised thymine, light dependant UV, cleaves T dimers —> error free
- pyrimidine only

Question 16

How does DNA methyl transferase rep mech work

Answer 16

Reverse action of alkylation by transferring methyl/ethyl groups from guanine and Thymine to an internal Cysteine residue on the enzyme

Question 17

Describe how the Glycosylate DNA reps mech works

Answer 17

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

Question 18

Name 3 types of specific DNA repair mechanism

Answer 18

Deoxydipyrimidine Photolyase
DNA Methyl Transferase
Glycosylate

Question 19

Name some general repair mechanisms

Answer 19

Proofreading ability of DNA p
SOS response
Suppression
Inherent resistance

Question 20

Describe the DNA polymerase proofreading ability

Answer 20

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

Question 21

What are 3 steps of DNA Polymerase proofreading

Answer 21

Endonuclease Cleavage
DNA gap filling
Ligation

Question 22

Describe the Exonuclease cleavage step of DNA Polymerase proofreading

Answer 22

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

Question 23

Describe the second step of DNA Polymerase proofreading

Answer 23

DNA gap filling. Polymerase uses free 3’-OH group in the gap to add sequential bases using intact strand as template.

Question 24

Describe the final step pf DNA polymerase proof reading

Answer 24

DNA ligation. 3’-OH Of new patch ligated to 5’-Phosphate terminus of original strand to give one DNA molecule

Question 25

What are the names of the two forms (Tautomers) a nucleotide can take

Answer 25

Keto & Enol

Question 26

What mechanisms respond to disruption in DNA replication e.g. by Thymine Dimers

Answer 26

SOS response: avoids cell death by suspending proofreading allowing replication to continue regardless (tries to withstand mutation)

Question 27

How does the Suppression DNA repair mechanism work

Answer 27

Suppresses affect of primary mutation e.g after deletion, it’ll insert a random base, may code for different codon but fixes frame shift and only affects one residue.
Some Anticodons can recognise and change pack missense mutations.

Question 28

What are some of the inherent traits of DNA allowing it to be resistant to mutation

Answer 28

2 identical strands allow it to be Accurate worked on.
One strand can always act as a template for the other
The structure makes detection and repair easy, every deamination event in DNA leads to recognition and removal as they turn into foreign bases