DNA Damage and Repair Flashcards
DNA damage occurs daily but how?
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
Most damage occurs during replication, how?
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
Complementary base pairing on template strand forms new strand but how can this go wrong?
DNA Polymerase sometimes might add wrong nucleotide leading to helix distortion,damaged base incorporation, and small deletions/insertions can occur
What are MMR proteins
Mismatch repair proteins that follow polymerase and proofread new strand which identify and remove mis incorporated nucleotides
Name 4 types of DNA damage
1.Depurination and deamination (most common)
2.Base oxidation
3.Base alkylation
4.DNA adducts and cross links- induced by chemicals or radiation
What do depurination (Purine) and deamination (Cytosine) affect?
Affect DNA bases due to random interactions between DNA and surrounding water molecules
What does base oxidation affect?
Usually affects C and G and induced by ROS
How can Base alkylation occur?
Can be accidentally caused by S-adenosyl methionine, an enzyme which transfers methyl groups which interfere eventually with replication
What are examples of mutagens?
Alcohol metabolites, ROS
Environmental mutagens: Air/water Pollutants, drugs, toxins, food preservatives
Radiation: UV, ionising radiation.
How are DNA adducts caused?
Usually caused by a chemical binding to DNA
Caused by aflatoxin and acetadlehyde - product of alcohol metabolism
Which interfere with replication
What are DNA cross links, how can they be caused and how are they bad?
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)
What anti cancer drugs can often cause DNA damage?
Topoisomerase inhibitors
Intercalating agents like cisplatin
And radiotherapy which breaks strands
What are the two general types of repair systems for DNA damage?
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
What can happen if DNA cannot be repaired?
1.Heritable change in the genetic material
2.mutations provide allelic variations - evolutionary change and can be harmful and often cause disease
Three main types of mutations?
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
What are point mutations?
Where one incorrect base may be added in first round of replication
2nd round of replication can lead to permanent mutation
What is a silent point mutation?
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
What is a neutral point mutation?
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
What is a missense point mutation?
Where mutated gene translation leads to production of a non functional protein
What is a nonsense point mutation?
Where mutated gene leads to translation of a short protein due to an accidental production of a stop codon
What can an insertion or deletion of a base pair mutation do?
Mutated gene during translation may produce or lose stop codons leading to possibly shorter/longer polypeptides
