4.4 Flashcards
Spontaneous DNA damage
Deamination of adenine, cytosine and guanine.
Depurination - loss of purine bases due to bond break between purine base and deoxyribose.
Induced DNA damage
Formation of pyrimidine dimers from UV light.
Alkylation - addition of methyl or ethyl groups to DNA bases
Carcinogens react with DNA bases causing addition of bulky chemicals groups to DNA.
Direct reversal repair
Used for pyrimidine dimers that result from UV light exposure and alkylated guanine residues.
Repair of pyrimidine dimers
Dimers distort DNA structure blocking transcription or replication. This is repaired by photoreactivation where energy from visible light used to split bonds formed in cyclobutane ring.
Repair of alkylated guanine residues
o6 methyl guanine methyltransferase transfers methyl group to cysteine residue
Base excision repair
Single damaged base removed and replaced
removal of incorrect base by DNA glycosylase.
nicking of damaged DNA strand by AP endonuclease upstream of AP site.
extension of 3’ OH terminus by DNA polymerase.
Nucleotide excision repair
oligonucleotide containing lesion is removed.
Helicase opens DNA double strand and nucleases cleave the lesion. Dna polymerase fills gap and is joined by ligase.
Xeroderma pigmentosum
Very sensitive to UV light.
Transcription coupled repair
Lesions in genes that are actively transcribed. When lesion is transcribed RNA polymerase stops and coupling factor(e coli) /CSA and CSB displaces RNA polymerase and recruits different proteins to cleave and repair area.
Cockayne syndrome
Mutation in genes that code for CSA and CSB. Alterations in genes are not repaired efficiently
Mismatch Repair
Recognises non complementary bases.
Enzymes identify and cleave the bases. Mammals MSH AND MLH for e.coli MUTH
Hereditary nonpolyposis correctal cancer
Mutations in MSH and MLH responsible.
Translesion DNA synthesis
When previous repair systems fail. polymerase 2,4,5 replace normal polymerase at point of damage and continue replication. Then at the end it is replaced by normal DNA polymerase.
Specialized DNA polymerases show low fidelity.
Double strand break repair
Repair carried out by non homologous end joining and homologous recombination.
Non homologous end joining the two broken ends of a chromosome are put back together but can cause a mutation.
Homologous recombination -
