Lecture 4 Flashcards
(10 cards)
Overcoming the effects of mutation (restoring function) can occur in 2 ways:
- Genetic ____
- Genetic ____ (more frequent.)
Genetic reversion
Genetic Suppression
Exact genetic reversion has not been observed in vivo. _____ genetic reversion is rare, but occurs in vivo and is defined as a misense mutation that reverts the amino acid coded for in the mRNA back to the original, though the codon is not the exact same as the original.
Equivalent
Genetic suppression can occur as intra or extra-genic. Intragenic means the second mutation occurs within the ____ ____, and restores partial function to the mutated gene product. Extragenic means the second mutation occurs in a gene whose product interacts with the mutated gene product from another gene, thus partially restoring their interaction.
Reading Frame
______ mosaicism is exemplified in the disease Junctional _______ Bullosa, due to a homozygous defect in the _____3 gene (codes for laminin-332). Phenotypic revertants arise from 2nd site ______ mutations (reversion is much rarer).
Somatic
Junctional Epidermolysis Bullosa
LAMB3
Suppressor mutation
There are 4 ways in which DNA replication mutations are avoided or corrected:
- Polymerase Selectivity –> shape of the polymerase disallows the incorrect nucleotide from moving into the appropriate site to be added.
- Polymerase Proofreading –> a function of the 3’ ______ activity of the polymerasae.
- Mismatch repair –> In bacteria, mismatch repair proteins recognize the new strand because it is not ______. In eukaryotes, the proteins recognize the new strand because it has _____ (present between Okazaki frags and where RNA primers were removed.)
- Collection of repair and error avoidance mechs.
3’ Exonuclease
Methylated
“Nicks”
____ rounds of replication are required for a mutation to be “fixed” (not fixed as in corrected, but rather set in place as a transversion mutation.) This should make sense given the semi-conservative nature of DNA replication.
2 rounds
Hereditary (Familial) Nonpolyposis Colon Cancer, aka _____ syndrome, is caused by an autosomal ______ inheritance of cancer PREDISPOSITION, so the affected individuals are initially heterozygous. Through somatic loss of heterozygosity (specifically loss of the wild type gene), the cancer forms.
Lynch syndrome
Dominant
DNA _____ is a thermodynamic property of DNA, whereby the ends of the DNA denature and renature. This can lead to an improper re-association of the strands, such that a looping out of one of the strands occurs. This occurs at ______ sequences. When the looping out or slippage occurs in the _____ strand, an extra base is added in the second round of replication. When it occurs in the _____ strand, the looped out base(s) are lost in the second round of replication.
Breathing
Repetitive
New strand
Template strand
There are four major examples of pro-mutagenic spontaneous DNA damage.
- Deamination occurs via hydrolysis (more readily in animals with 37 degree C body temp) and results in conversion of _____ to uracil (leads to a tranversion mutation after second round of replication).
- Oxidation result from ROS, and converts _____ to 8-___-_____. This is the most significant mutagenic DNA damage inflicted by oxygen radicals (leads to a tranversion mutation after second round of replication).
- Depurination –> leads to an ______ site, but the DNA _____ is intact (3/4 of the time, the wrong nucleotide is incorporated - should make sense statistically if there are 4 possible nucleotides).
- Incorporation of ____ nucleotides (instead of dNTPs) –> leads to DNA strand breaks and is the most significant source of DNA damage.
Cytosine
Guanine
8-oxo-guanine
Abasic
Backbone
Ribonucleotides (NTPs)
8-___-____ flips to a ____ conformation from a normally _____ conformation (which all normal nucleotides exhibit.) This causes a mismatch with Adenine, forming what’s called “Hoogsteen Pairing.”
8-oxo-guanine
Syn
Anti
