Lecture 8 Flashcards
cancer
a build up of many mutations
-the longer you live the more you mutate therefore increasing your risk of cancer
oncogene active
can mutate the p53 gene which will lead to the mutated growth of malignant tumors
mutations in a person affect the next generation true or false
false because the mutations in their body cells only affect them
mutations in sperm or eggs affect the next generation true or false
true because if the mutation is in the egg or sperm it will get passed down to the offspring
why do male make more mutations
because they make more sperm than females make eggs
-men have a high chance for autism and schitzophrenia
point mutation
one base is affected
-one change in nucleotide (nucleotide substitution) or an indel (insertion or deletion and not silent)
a silent mutation
-can be a point mutation
-does not change the amino acid being encoded
why do point mutations not cause a change in the amino acid
because the genetic code is redundant and therefore a single change does not necessarily change the aa being encoded because there are many base sequences encoding for the same aa
missence mutation
a change in the DNA that results in a change in the amino acid being encoded
-can result from nucleotide substition, indel etc
inversion
dna turned backwards
nonsense
base is converted into a stop codon
-results in a truncated protein
promotor
turns on a gene
-RNA pol binding site
-a mutation here is outside the coding sequence
termination signal mutation
-this signal will stop RNA synthesis
-this mutation is outside the coding sequence
splice donor and acceptor mutation
causes a misprocessing of RNA
-mutation outside the coding sequence
ribosome binding site mutation
turns the binding site into a 5 prime untranslated region where the ribosome will not be able to recognize it
-this is outside the coding sequence
chromosome rearrangement
-not genetic mutation bc it is not on the coding sequence or
-three types: translocation, deletion and duplication
-this happens to the whole chromosome
transition
-a point mutation that can be silence or missence where a purine (two ring A or G) is converted to a pyrimidine (C or T) or vice versa
-change base with a base of similar shape
-a type of nucleotide substitution
-stay on the same road but change lanes
-this will not change the base pair is A becomes T or C becomes G
-the base on the lagging strand will change in response to become a base pair match
transversion
-changing a purine (AG) for a purine or a prymidine (CT) for a prymidine
-a type of nucloetide substitution
-this will change the base pair
what mutation causes sickle cell anemia
a missense mutation that makes lys become glu
giesma stain
stains DNA so you can karyotype it
nondisjunction
mispackaging of chromosomes during gamete production
-one gamete will get no chromosomes
-if nondisjunction has a female it will die (XXX)
-XXY can live
-happens in meiosis 1 or 2
Indel
can shift frame of coding region messing up the amino acid after it resulting in a truncated protein or missense (useless)
-causes ribosome to make the wrong amino acid because of the frame shift
what does nondisjunction create?
aneuploidy= abnormal chromosomes
-monozomic or trisonomic (cause of trisonomy)
polyploidy
2 or more complete sets of chromosomes
-this is more likley than aneuploidy
-tri can happen in humans
-tetra can lead to a new species (plants)
will chromosome rearrangment affect the chromosome number
no
if female gives an xx egg from nondisjunction what happens when it gets w sperm
if the sperm donates an x the egg dies if a sperm donates a y it can live
-females from nondisjunction only survive if the femal gives a 0 egg and the X comes from the sperm
XO nondisjunction in humans
causes Turner syndrome
-sterile
XXY in human
kleinfel syndrom
-sterile
autosome nondisjunction
-disjunction that does not involve the sex chromosomes
-ex: down syndrome from an extra chromosome 21 (47n)
-the older the mother the more likely this is because as you age you have less control over meiosis
change in chromosome banding patterns
-deletion, duplication, inversion and translocation (chromosomal rearrangement so it is a mutation outside of the coding sequence)
-these mutations will effect how genes are expressed in the coding sequence)
deletion
removing a chunk of chromosome
duplication
duplicating a chunk of chormosome
-inversion
inversion
entire chunk is reversed
translocation
a chunk is taken from one chromosome to another
what causes an indel mutation
-looping out of the strand during replication causing polymerase to skip bases on the templet (deletion)
-looping out of daughter causes polymerase to put extra base on daughter and when it is elongated it is too long
substitution is caused by?
DNA pol making a mistake
-this may cause a buldge in the backbone bc the bases on the strand don’t fit together
-this misincorporation can affect and pass on to offspring
-can also be caused by base tautomeric forms
tautomeric forms
same base but different H bond pattern
ex: A is normally NH2 but tautomeric will be NH and NH
-this changes the acceptor and donator characteristics of the base cause pol to give it the wrong base
ex: A prime (tautomeric) will not fit with C and not T= mismatch
how does dna differentiate btwn daughter and template
template adenine gets methylated before daughter so this lets DNA pol identify daughter and find mistakes in prokaryotes bc they are circular
-maybe eukaryotes use the gaps in the daughter strands
can DNA fix a buldge
yes by activating 3 to 5 exonuclease that will go backward on the strand and fix the mistake
MUTS
will bind to the mismatch on both strands/ binds to the buldge
-has the error and therefore lets pol know the template is the outerstrand
MUTH and L
bind to the daughter strand
-forms tertiary complex with MUTS when the fold over creating a loop
exonuclease
is the pacman that will chew up the error on the inner daughter strand letting DNA pol remake that chunk fo daughter
spontaneous deanimation
cytosine becomes uracil because it looses NH2 for an oxygen
-this causes an A to go on the opposite lagging strand
How is spontaneous deanimation corrected
dna glycosidase finds the uracil and removes it by flipping out the DNA and removing it
-this leaves an abasic site that can be chewed up by abasic specific endonuclease
-pol then makes it again
base modification chemicals
chance DNA base by giving mutations to daughter
ex: nitrous acids in food will turn C to G and G to T
Hydroxylamine
adds hydroxyl to DNA base to cause misincorporatio
-changes C to G on template so the daughter strand gets a C and not a G
alkanating bases
add alkyl groups to cause misoncorporation
intercalators
insert intercalates between bases on the DNA which causes a change in shape causes pol to miss bases which leads to indels
AMES
test to detect mutagens
ex: salmonella will not grow without histidine media and rat liver broth w a mutagen. A plate without the mutagen will have minimal growth which proves that the mutagen can grow w out histidine)
-point of the test is to look for mutation that increase the cells ability to grow without histidine
radiation/ x ray
ions causing breaks in the double strand that can also cause translocations to other chromosomes
-fix by: non homologous end joining (join broken ends) or homologous recombination (recombine broken chromosome with the other parents non broke chromosome)
why are some bacteria resistant to radiation
because they have many homologous machinery enzymes to fix breaks
UV
-nonionizing radiation that doesn’t break double strands it just causes covalent dimerization
-dimerization changes shape, ridgidity and ability to detect mistakes
-fixed by UVr pathway
how is UV damage fixed
-UVAB finds thiamine dimer
_UVRB and UVRC make a complex that cuts the side of the dimer on the defective strand
-DNA pol will fill gap
-ligase will seal it
mutates DNA repair enzymes can increase what?
risk of cancer because you cant fix DNA mutations well
