Flashcards in Lecture 12 Deck (22):
what percent of genetic diseases are due to missense mutations?
what percent of genetic diseases are due to nonsense mutations?
what percent of genetic diseases are due to addition/deletion mutations?
what percent of genetic diseases are due to RNA splicing mutations?
what is the difference between and exact reversion and an equivalent reversion?
exact results in the exact same codon as the original protein, equivalent results in a different codon that still codes for the original protein (GAG vs GAA for Glu)
what is the difference between an intragenic mutation and an extragenic mutation?
- an intragenic mutation is a suppressor mutation that occurs on the same gene as the original mutation.
- an extragenic mutation is a suppressor mutation that occurs elsewhere in the genome but has an effect that alleviates the primary mutation.
what is a suppressor mutation?
it is a secondary mutation that alleviates or reverts the phenotypic effect of a primary mutation
what are most phenotypic reversions are usually due to?
genetic suppression at a different site within the same gene or another gene altogether.
- rarely every an exact reversion
what are four routes for acquiring spontaneous mutations?
1 - polymerase errors on normal templates that escape fidelity checks
2 - misreplication at repetitive sites due to to strand slippage
3 - misreplication at damaged template sites
4 - transposable genetic elements
what are the four forms of fidelity checks?
1) high polymerase selectivity
2) polymerase proofreading
3) post-replication mismatch repair
4) repair and error-avoidance mechanisms
how is the parental strand of DNA distinguished from a newly replicated daughter strand?
parental stand is fully methylated while the daughter strand is hemi-methylated
what are the steps for mismatch repair?
- MutS binds to mismatched DNA, recruits MutL
- MutL activates endonuclease MutH
- MutH binds hemimethylated GATC (dam) site and nicks daughter strand
- helicase and an exonuclease start at this nick and remove surrounding sequence including mismatch
- DNA Polymerase fills the gap
what is the overall error rate of DNA Synthesis?
10 to the negative 10
what is the error rate of polymerase selectivity?
10 to the negative 5
what is the error rate of proofreading and post-replication mismatch repair, respectively?
10 to the negative 2 for both
what occurs in Lynch Syndrome?
- mutation in the genes coding for mismatch repair
what is another name for lynch syndrome?
HNPCC (hereditary non-polyposis colon cancer)
what is the most mutagenic DNA lesion produced by oxygen radicals?
what does 8-oxoguanine bind to and why?
- adenine instead of cytosine
- imadizole part of the purine gets oxidized, removing a bond from the nitrogen closest to the carboxyl group. This nitrogen gains a hydrogen which allows it to now hydrogen bond.
what makes transposable genetic elements mutagenic?
- if a transposon jumps and inserts within a gene it will deactivate that gene.
What is DNA breathing?
The continuous unannealing and reannealing of DNA strands from each other. Can result in slippage.