Flashcards in Lecture 49 Deck (18)
what are the short-term consequences of DNA damage?
1. reduced proliferation
2. altered gene expression
what are the long term consequences of DNA damage?
What are the two classes of spontaneous mutation?
1. errors of replication
2. spontaneous lesions- chemical changes
what kind of errors can occur during replication?
wrong base is incorporated by DNA poly
due to tautomerism sometimes thymine can be in its enol form and bind with guanine
what is bloom syndrome?
A defect in the DNA helicase enzyme
1. smaller than average
2. narrow chin, prominent nose and ears
3. facial rash
4. chromosome instability (higher risk of cancer)
What are the three main types of spontaneous dna damage?
3. oxidative damage
breaking of glycosidic bond between base and sugar in purine nucleotides; a purine is lost
An apurinic site is the result
loss of an amine group from a base
cytosine will deaminate to uracil
but... 5-methyl cytosine deaminates to thymine; which will lead to bigger issues. (mutational hotspot)
explain oxidative damage?
a result of the production of reactive oxidative compounds due to oxidative metabolism
can lead to a transverse mutation
what can UV light lead to the creation of?
covalent linkages between adjacent pyrimdine bases on the same DNA strand.
these dimers interfere with normal base pairing and block replication
types of repair mechanisms?
1. nucleotide excision
2. base excision
3. mismatch repair
How does excision repair occur?
1. recognize damage
2. recruit endonucleases
3. region excised
4. DNA poly fills gap
5. ligase seals
autosomal recessive disorder
mutations in NER genes
base pair excision?
1. missplaced base
2. base removed by glycosylase
3. sugar phosphate removed by endonuclease
4. replace base and ligate
1) Mismatch missed by proofreading is recognized by MSH proteins
2) Repair may occur during S-phase (if missed by proof-reading) or in G2 when genome is scanned for errors
3) Excision of bases around mismatch
4) Repair by re-synthesis
how can double strand breaks be fixed?
1. non-homologous end joining
2. recombinational repair
what is the result of DNA repair gene mutation?
1. increased error rate
2. genomic stability