DNA repair and damage Flashcards
(24 cards)
What is a telomere?
Repetitive sequence of nucleotides at the end of each chromosome - TTAGGG
Acts as a buffer - the telomere sequence is degraded rather than genes
How many time does the telomere sequence repeat?
Telomere sequence repeats 2500 times
How many bases do somatic cells loose each day?
Somatic cells lose 26 bases daily from telomere
What is the result of shortened telomeres?
Shortened telomeres = cell degredation and death
Where are telomeres found?
Telomeres are only found in eukaryotes as they have linear chromosomes (ends which can be degraded)
How do telomeres prevent degradation?
Telomeres prevent a DNA protein complex from TRF2 and telomere binding proteins
What is telomerase? Where is it found?
Found in germ, stem and malignent cells - NOT FOUND IN SOMATIC CELLS
Telomerase maintains the chromosome by adding TTAGGG repeats to the end of the chromosome.
DNA Pol and RNA primase are needed to add the telomerase repeats.
What are the different forms of DNA damage? Are they endogenous or exogenous
Endogenous damage - replication errors and cell metabolism
Exogenous damage - UV light, ionizing radiation, chemical exposure
How do inspection repair enzymes repair DNA?
Inspection repair enzymes:
Detect damage
Use undamaged nucleotide on complementary strand as a template for replacing damaged nucleotides
What proofreads DNA?
DNA polymerase proofreads DNA
What is meant by NER? Describe the steps
Nucleoside Excision Repair:
- DNA pol recognizes mistake in non-methylated daughter strand
- 3’ to 5’ exonuclease removes error nucleotides
- DNA polymerase aligns and joins correct nucleotides together
- DNA ligase inserts the correct sequence
Describe mismatch repair
When the wrong base in produced in the unmethylated daughter strand, it can be compared with the parent strand. It can then be repaired by mismatch repair enzymes
How do mismatch repair enzymes recognize the daughter strand?
The daughter strand is not methylated (no CH3 added)
What are the most chemically reactive elements in DNA?
N or C in nitrogenous base rings are very reactive
How do chemical reactions affect DNA?
Lesions are created:
Lesions can prevent replication
Lesions can cause mutagenesis - the lesion is replicated and becomes fixed in DNA forever
Lesions may block transcription or translation
Describe spontaneous DNA damage
Spontaneous damage causes deamination of bases e.g. when cytosine is deaminated, uracil is formed. Uracil binds to adenine rather than guanine
How is spontaneous damage repaired?
BAR - Base excision repair
Describe BER
- DNA glycolase breaks glycosidic bond between deaminated base and sugar
- Exonuclease cleaves DNA at the site, creating a larger gap
- DNA polymerase links the correct deoxynucleotides together and DNA ligase inserts the missing bases into the chain
Describe depurination
Depurination:
Glycosidic bond between purine bases (A or G) and sugar is hydrolysed, casuing the purine base to be lost
How many purines are lost per cell per hour?
10,000 purines lost per cell per hour by depurination
How is depurination repaired?
NER
Describe pyrimidination
Glycosidic bond between pyrimidine (C or T) and sugar is lost
occurs less frequently than depurination
What are bulky lesions/adducts caused by?
UV light causes pyrimidine dimer formation - adjacent C or T bases on same strand link together.
Where the dimers/lesions occur, localised denaturation of DNA also occurs as the dimers cannot pair with opposite bases.
Bulky lesions are repaired by NER
Where is reactive O2 produced?
Aerobic metabolism causes reactive O2 to be produced via the fenton reaction
Reactive O2 attacks DNA
