DNA Damage and Repair

Question 1

DNA damage occurs daily but how?

Answer 1

Can occur spontaneously
Can occur In response to mutagens
Cells are equips with mechanisms of DNA repair and if not repaired leads to a mutation

Question 2

Most damage occurs during replication, how?

Answer 2

Single stranded DNA is prone to breakage (Phosphodiester bond)
Which can lead to bases being exposed to damaging agents leading to polymerase 3 fuckin up its flow

Question 3

Complementary base pairing on template strand forms new strand but how can this go wrong?

Answer 3

DNA Polymerase sometimes might add wrong nucleotide leading to helix distortion,damaged base incorporation, and small deletions/insertions can occur

Question 4

What are MMR proteins

Answer 4

Mismatch repair proteins that follow polymerase and proofread new strand which identify and remove mis incorporated nucleotides

Question 5

Name 4 types of DNA damage

Answer 5

1.Depurination and deamination (most common)
2.Base oxidation
3.Base alkylation
4.DNA adducts and cross links- induced by chemicals or radiation

Question 6

What do depurination (Purine) and deamination (Cytosine) affect?

Answer 6

Affect DNA bases due to random interactions between DNA and surrounding water molecules

Question 7

What does base oxidation affect?

Answer 7

Usually affects C and G and induced by ROS

Question 8

How can Base alkylation occur?

Answer 8

Can be accidentally caused by S-adenosyl methionine, an enzyme which transfers methyl groups which interfere eventually with replication

Question 9

What are examples of mutagens?

Answer 9

Alcohol metabolites, ROS

Environmental mutagens: Air/water Pollutants, drugs, toxins, food preservatives

Radiation: UV, ionising radiation.

Question 10

How are DNA adducts caused?

Answer 10

Usually caused by a chemical binding to DNA
Caused by aflatoxin and acetadlehyde - product of alcohol metabolism
Which interfere with replication

Question 11

What are DNA cross links, how can they be caused and how are they bad?

Answer 11

Cross links can be formed between two strands or within one strand which prevent DNA unwinding for replication and transcription

Caused by UV and some drugs (anti-cancer)

Question 12

What anti cancer drugs can often cause DNA damage?

Answer 12

Topoisomerase inhibitors
Intercalating agents like cisplatin
And radiotherapy which breaks strands

Question 13

What are the two general types of repair systems for DNA damage?

Answer 13

1.Direct reversal systems-correct damaged areas by reversing damage
2.Excision repair system - cuts out damage and repairs gap via DNA synthesis and ligation

Question 14

What can happen if DNA cannot be repaired?

Answer 14

1.Heritable change in the genetic material
2.mutations provide allelic variations - evolutionary change and can be harmful and often cause disease

Question 15

Three main types of mutations?

Answer 15

1.Chromosome mutations - changes in chromy structure
2. Genome mutations -changes in chromosome numbers
3. Gene mutations - small changes in DNA structure which affect a single gene

Question 16

What are point mutations?

Answer 16

Where one incorrect base may be added in first round of replication

2nd round of replication can lead to permanent mutation

Question 17

What is a silent point mutation?

Answer 17

During translation a base pair may be translated differently however it may lead to the same protein being produced (genetic code is degenerate) leading to no change in the end

Question 18

What is a neutral point mutation?

Answer 18

Where mutated gene is translated and a protein with similar properties is added to a polypeptide, and there is no detectable change in the end

Question 19

What is a missense point mutation?

Answer 19

Where mutated gene translation leads to production of a non functional protein

Question 20

What is a nonsense point mutation?

Answer 20

Where mutated gene leads to translation of a short protein due to an accidental production of a stop codon

Question 21

What can an insertion or deletion of a base pair mutation do?

Answer 21

Mutated gene during translation may produce or lose stop codons leading to possibly shorter/longer polypeptides