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182 Cards in this Set
- Front
- Back
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2 major proc resp for gen variat?
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1. mutat
2. recombinat |
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mutation ______________ playing cards, and ___________________ recombination ____________ playing cards
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mutat introduces
recombinat shuffles them |
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mutagens
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cause mutations
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excision repair
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damamged dna strand is cut out, oth strand is used as templ to remake the damaged one
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what is the minimum mutat that can be induced?
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point mutation
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t or f
its easier to have a loss of funct mutat than a gain of funct mutation |
t
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new mutat are categorized as/
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1. induced
2. spontaneous |
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what is rate of spont mutat?
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one c in 10^5 to 10^8
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mutagenesis
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prod of mutat thr expos to mutagens
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an organ that has gone thr mutagenesis has been?
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mutagenized
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mutagens have a ______________ dose response
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linear
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there is always a ___________ level of mutations, even when you are inducing mutations on purpose
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background level
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2 main types of point mutat are?
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1. base subst
2. base addit or delet |
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base substit are what 2 kinds?
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1. transition
2. tranvservion |
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transition point mutat is?
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replacement of A with G
or T with C |
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replacing a purin with a purin in a mutat is?
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transition mut
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replac a pyrimidine w a pyrimidine is a?
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transition mut
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transversion point mutat is?
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replac of purine w a pyrimidine
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purines are?
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A and G
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pyrimidines are?
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C and T
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indel mutat are?
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insertion deletion mutat
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addit or delet mutat are actually?
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addit or mutat of nucleotide pairs
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mutat at prot level
a mutat that leads to a diff codon that encodes the same original AA is? |
a synonymous mutation
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synonymous mutat are also called?
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silent mutat
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missense mutation is?
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codon for one aa is changed to a codon for another aa
also called nonsynonymous mutat |
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nonsense mutat are?
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codon for one aa is ch to a stop codon
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synonymous mutat never alter?
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the aa seq of polypeptide chain
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conservative substit (from a missense mutat)
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when an aa is repl wit a chemically similar one
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nonconservative substitution (from a missense mutat) is
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when an aa is repl w a chem non similar other aa
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nonconservat are more likely to prod _______________- in prot struc and funct
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severe changes
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the closer a nonsense mutat is to the ______________ end of open reading frame the _____________
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3' end
more likely that result prot will stil have some biolog activit |
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nonsense mutat lead to?
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premat terminat of translat
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indel mutat _________ the reading frame
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changes
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indel mutation leads to a ___________
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frameshift mutation
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frameshift mutat is caused by?
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an indel mutat
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t or f
you can also have mutations in noncoding an regulatory dna like promoters |
t
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you can have mutat in regulatory regions of dna that can change the level?
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of express of a g
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just bec you have a mutat on the genotypic leve does not mean you will have one?
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on the phenotypic lev
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northern blot looks at?
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rna
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western blot looks at
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protein
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mutational specificity
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mutag tend to do a cert kind of mutat and at a certain spot called hot spot
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hot spot
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place where a cert mutag tends to makes its mutations
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mutagents
3 mech? |
1. replace a base
2. alter a base 3. damage a base |
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base analogs
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chemic comp that are so similar to normal nitr bases of dna they are accid incorp into dna struct
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tautomers of bases
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the diff forms of dna bases that they can naturally take
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tautomers of bases
what are the diff forms? |
1. keto
2. imino 3. enol |
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keto, imino, enol
which one is the most common? |
keto
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what is the change of one tautomer into another called?
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tautomeric shift
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when a dna base bec ionized it can?
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cause a mispair
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if A bec its rare imino form it could accid pair w?
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C instead of T
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name 2 mutagens that alter a base?
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EMS and NG
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EMS is?
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ethylmethanesulfonate
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NG is?
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nitrosoguanidine
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EMS does what to the DnA bases?
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it adds an ethyl gr
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EMS and NG both add?
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alkyl gr to differ positions on the bases
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base alteration
when is a mutat most likely to occur? |
when the alkyl gr is added to the oxy at posit 6 of guanine to make o-6-alkylguanine
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adding an O to posit 6 of guanine leads to what transition?
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G C ---> A T
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T or F
alkylating agents can ch incoming bases during DNA synth |
T
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name 3 types of incalating agents?
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1. proflavin
2. acridine orange 3. ICR compounds |
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intercalating agents do what?
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flat planar molecules that mimic base pairs and can slip betw nitrogen bases
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an intercalating agent like acridine orange
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what caused this to happen
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acridine orange, ICR-191, proflavin can cause ___________ in the DNA
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single nucleotide pair insertions or deletions
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if a mutag damages a DNA base it can ___________ DNA synthesis
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block
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E COli uses what system to bypass a damaged DNA base?
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SOS system
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t or f
SOS is used only as a last resort |
t
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DinB , UmuC, and UmuD' are ?
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error prone DNA polymerases
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EP polymerases are also called?
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sloppy copiers or error prone polymerases
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the eukaryote system _____________ is similar to E Coli SOS system
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translesion DNA synthesis
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how do EP polymerases overcome the block in replica?
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they add nucleotides to the strand opposite the damaged bases
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t or f
error prone polymerases are always present in euk cells |
t
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error prone polym in E Coli only appear when?
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they are induced to by UV damage
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SOS mechan
UV light induces the synth of what protein? |
RecA
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REC A is a key player in?
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mechan of DNA repair and recombination
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e coli
dna damage DNA polymerase ________ stalls at site of dna damage |
III
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e coli
dna ahead of DNA pol III is unwound and bound by ______, and then ___________- |
SSB
and then RecA |
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Rec A and SSB join to form?
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protein DNA filament
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nist carcinogens like uv and aflatoxin B1 are ___________ mutagens
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SOS dependent
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name one uv light generated photoproduct?
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cyclobutyl ring that unites adj pyrimidines
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UV light makes what alterations in DNA?
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photoproducts
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what is most freq transition causes by UV light?
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C ---> T
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Aflatoxin B1 comes from?
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a fungus assoc w peanuts
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apurinic site is where?
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in DNA, where the base and the sugar backbone have been separated..
happens with aflatoxin |
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aflatoxin B1 causes what kind of mutation?
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G -C --> T-A transversion
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Luria and Delbruck tested?
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e coli to with phage T1 to see if any would bec resistant
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luria and delbruck
were testing to see if? |
the mutations were random or induced by the phage
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who came up with the "fluctuation test"
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luria and delbruck
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luria and delbruck
their experiment suggested that? |
resistant e coli cells are select by environm agent (the phage) but not produced by it
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replica plating reveals mutant colonies on a __________ thr their behavior on __________
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master plate
selective replica plates |
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replica plating can be used to screen for mutants that?
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fail to grow under selective regime
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spontaneous lesions are?
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naturally occuring damage to dna
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what are 2 most freq spont lesions?
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depurination and deamination
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which is the more common spont lesion , depurination or deamination?
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depurination
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deamination of cytosine yields?
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uracil.
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deamination of 5-methylcytosine generates?
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thymine. making a C to T transition
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DNA analysis of "hot spots" for mutations freq show what base is there?
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5-methylcytosine residues
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what is another type of spont lesion?
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oxidatively damaged bases
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name 3 active oxygen species?
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O2-, H2O2, and OH radicals
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errors in dna replicat can cause?
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base substitut
base insert and deletion |
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in e coli indel can occur at?
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repeated seq in dna
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e coli
longer repeats are hot spots for? |
deletions
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common mech respons for genetic diseases is?
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expansion of a 3 base pair repeat. called trinucleotide repeat disease.
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what is an ex of a trinucleotide repeat disease?
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fragile X syndrome
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errors in dna replicat can cause?
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base substitut
base insert and deletion |
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in e coli indel can occur at?
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repeated seq in dna
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e coli
longer repeats are hot spots for? |
deletions
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common mech respons for genetic diseases is?
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expansion of a 3 base pair repeat. called trinucleotide repeat disease.
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what is an ex of a trinucleotide repeat disease?
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fragile X syndrome
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fragile x syndrome results from?
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changes in number of a (CCG)n repeat in a region of the FMR-1 gene
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(CCG)n repeat in a region of the FMR-1 gene
parents and grandp have increased numb of the repeat so they have? |
premutations. cause they dont have the dis yet but they do have increased copy number
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fragile X syndrome
(CCG)n repeat in a region of the FMR-1 gene if you have premutations what will happen? |
the repeats will increase a lot more in your offspring
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fragile X syndrome
(CCG)n repeat in a region of the FMR-1 gene what is proposed mechanism? |
slipped mispairing in course of DNA synth
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Huntington disease is assoc with?
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expansion of trinucleotide repeats in a g. huntingtons dis has a repeated seq, often within prot coding regions
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Huntington disease and Kennedy disease result from?
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amplification of a 3 base pair repeat of CAG
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fragile X syndrome
6-59 number of copies. phenotype? |
normal
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fragile X syndrome
60-200 number of copies. phenotype ? |
largely normal. this is the premutation stage
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fragile X syndrome
>200 number of copies. phenotype IS? |
AFFECTED
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FMR-1 g, that are involved in fragile x syndrome, are freq ______ , which is assoc with silenced genes
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hypermethylated
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dna error free repair
what are 2 ways this happens? |
1. repair the damaged base
2. delete the damaged dna and use complem seq as template |
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direct rev of damag dna
which dam can be revers? |
a photodimer caused by uv light
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photolyase can repair?
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a photodimer caused by uv light
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light repair or photorepair uses what enzyme?
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photolyase.
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why is photolyase a photorepair enzyme?
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bec you need cert wavelenghts of light for it to work and repair the damag dna
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t or f
photolyase can not work in the dark |
t
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name 2 dna repair enzymes
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1. photolyase
2. alkyltransferase |
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alkyltransferase is a ?
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dna repair enzyme. they can remove alkyl gr from damaged dna
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what are 3 types of repair with dam dna?
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1. direct rev
2. base excision and replac 3. segm removal and replacement |
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what are 2 types of homology depend repair systems?
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1. excision repair
2. postreplication repair |
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homolog dep repair syst
excision repair occurs? |
before replication
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homolog dep repair systems
depend on _____________ of the DNA |
complementarity
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excision is the ____________ of an entire base
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removal and replacement
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what enzyme carries out base excision repair?
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DNA glycosylase
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DNA glycosylase cleaves?
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base-sugar bonds
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DNA glycosylase generates ___________ sites
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apurinic or apyrimidinic
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dna glycosylase works with what enzymes?
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ap endonuclease
deoxyribophosphodiesterase dna polymerase dna ligase |
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what does ap endonuclease do?
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it cuts the sugar phosphate backbone around the site lacking a base
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base excision repair ends with _____________ sealing the repaired DNA
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dna ligase
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there are more ways to damage a base in dna than?
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there are glycosylases to remove them. so instead you have to use nucleotide excision repair
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nucleotide excision repair system detects?
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distortions in the double helix
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nucleotide excision repair
e coli 3 enzymes will? |
cut the damaged str at 2 sites flanking the lesion
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nucleotide excision repair
e coli the uvr exinuclease cuts out? |
8 nucleotides from one side
and 4 from the other |
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euk
yeasts nucleotide excision repair is done by? |
repairosome
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euk
yeasts repairosome preferentially repairs ? |
the template, or transcribed DNA strand
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euk
yeasts repairosome has subunits that are also subunits in the? |
basal rna transcription apparatus
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name one post replication repair?
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mismatch- repair system
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mismatch repair system has to do what 3 things?
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1. recog mismatched base pairs
2. determ which base is the wrong one 3. excise the incorr base and carry out repair synth |
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replication errors produce errors on which strand?
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the new strand
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t or f
normally bacterial dna is methylated |
t
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post replicat repair
right after replication, the new bact dna is has not yet been? |
methylated
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post replic repair
e coli adenine methylase does what? |
it methylates the dna strands.
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post replicat repair
e coli mismatch repair system can work bec it can dist the old strand from the new one by? |
the methylation pattern
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mismatch repair in hum
it repairs freq errors in what? |
short repeat seq (microsatellites)
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humans
short repeat seq are also called? |
microsatellites
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hMutSα and HMutLα fix what kinds of mismatch?
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mispaired regions and loops
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prok
mismatch repair system corrects errors in replication that are not corrected by? |
proofreading function of the replicative dna polymerase.
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prok
mismatch repair system it only fixes the? |
newly synthesized strand
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repair of ds breaks
how does this occur? |
if both str of double helix break at sites that are close to each other
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making ds breaks is a normal part of what in a human?
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generating antibod diversity
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give 2 examples of normal ds breaks?
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1. generating antibod divers
2. meiotic recombination |
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what 2 mech are used to repair ds breaks?
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1. non homologous end joining
2. homologous recombination |
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why is ds repair so hard in a non dividing cell?
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bec you dont have anything else to compare it to, like a sister chromatid
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ds break
if you dont put the ends back together what could happen? |
they could initiate chromosomal rearrangements
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non homologous end joining is?
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putting the ends back together of a ds break
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ds break
what is the proc? |
1. KU70, KU80, DNA dep prot kin bind
2 ends are trimmed 3. ends are joined 3 |
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what 3 proteins bind ds in a ds break?
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KU70
KU80 large DNA dependeint Prot kinase |
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homologous recombination is error free bec?
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it uses the sister chromatid to repair ds breaks
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homolog recombinat
first step? |
trimming of 5' ends
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homolog recomb
sec step? |
broken dna is coated with proteins including RAD51 (a RecA homolog)
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RAD51 is involved in?
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homolog recombination
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RAD51-DNA filament does what after its formed?
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searches for the undamaged sequence in its sister chromatid
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homol recombin
when RAD51-DNA finds the complementary reg on the sister chrom, what forms? |
joint molecule betw the the damaged sister chrom and the undamag sister chromatid
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what proteins are involved in repair by homolog recombinat?
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1. RAD51
2. DNA Polymerase 3. DNA ligase |
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In meiosis you can use
a. nonhomologous endjoining b. homologous recombination |
b. homolog recombination
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meiosis
crossing over is initiated by? |
a ds break
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molec mech of crossing over involves what 2 mech?
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1. ds break
2. format of heteroduplex DNA |
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heteroduplex dna is made up of?
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one DNA str from one parent and one from another
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first evidence for heteroduplex dna came from?
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strange ratios in fungi.
in their ascus. You should have ratio of A:a of 4:4 but you sometimes got 6:2 2:6 |
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what were the aberrant ratios seen in the fungi ascus?
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6:2, 2:6
5:3, 3:5 |
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when the ascus had extra copies it was said to have undergone?
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gene conversion
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ds break model of crossing over
what is the holiday structure? |
the formation of what looks like 2 single stranded cross overs
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fungus
ascus ds model of break crossing over holiday structure are resolved in what ways? |
1. vetical breakage
2. horizontal breakage |
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fungus
ascus ds break model if you had no A/a repair you would have a? |
5:3 octad
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fungus
ascus ds break model if you had A/a repair you would have a? |
6:2 octad
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