Week 2: Dna Damage And Repair Flashcards
What is a mutation?
Any change from the normal DNA sequence
Includes deletions, insertions, and substitutions.
What are the three types of mutations?
- Deletions
- Insertions
- Substitutions
What are transitions in mutations?
- Purine to purine (e.g. A to G)
- Pyrimidine to pyrimidine (e.g. C to T)
What are transversions in mutations?
Purine to pyrimidine (or vice versa)
What are the consequences of high numbers of mutations in the germ line?
They would destroy the species.
What are the consequences of high numbers of mutations in somatic cells?
They would destroy the individual organism.
What are exogenous sources of DNA damage?
- Ionising radiation (e.g. X-rays)
- UV light (sunlight)
- Chemicals (e.g. hydrocarbons in cigarette smoke)
What type of DNA damage is caused by UV light?
Thymine cross-linking (thymine dimers)
What are endogenous sources of DNA damage?
- DNA replication errors
- Hydrolysis
- Spontaneous depurination
- Spontaneous deamination
- Oxidation
What is depurination?
The removal of guanine or adenine from DNA.
What is deamination?
The conversion of cytosine to uracil.
What are reactive oxygen species (ROS)?
Normal metabolic by-products of respiration that can cause DNA damage.
What is the most frequent spontaneous chemical reaction creating serious DNA damage?
Depurination and deamination.
What are the consequences of DNA damage?
- Cell death
- Functional decline of tissues
- Cancer
- Developmental deficiencies
- Embryonic lethality
What is the proofreading activity of DNA polymerase?
A mechanism that helps correct errors during DNA replication.
What does Base Excision Repair (BER) do?
Removes single damaged bases.
What is Nucleotide Excision Repair (NER)?
Removes thymine dimers and large chemical adducts.
What is Mismatch Repair (MMR)?
Removes mismatched base pairs and insertion/deletion loops.
What is Non-homologous end joining (NHEJ)?
Repairs double-strand breaks (DSB) by joining broken ends regardless of sequence.
What is Homologous recombination repair (HR)?
Repairs double-strand breaks (DSB) using a sister chromatid.
What are the common themes of DNA repair?
- Detect the damage
- Remove the damage
- Resynthesis/Repair
- Regulation
True or False: Failure to repair DNA damage can result in cell death.
True.
What genetic disorders are associated with defective repair mechanisms?
- Xeroderma pigmentosa (UV sensitivity)
- Hereditary nonpolyposis colon cancer (HNPCC)
- Bloom syndrome (premature aging)
What role does BRCA1 play in DNA repair?
Involved in both checkpoint arrest and double-stranded DNA repair.
Fill in the blank: The process of removing methyl groups from DNA is performed by _______.
O6-methylguanine-DNA methyltransferase.
How often does depurination occur in nucleated human cells?
Each nucleated human cell loses ~5,000 DNA purines per day.
What is oxidative damage in DNA?
Damage caused by reactive oxygen species attacking purine and pyrimidine rings.
