Lecture 21 Flashcards
progeria = mutation in lamin-encoding gene
3 genes encode lamin proteins
LMNA LMNB1 and LMNB2
progeria = mutations in LMNA
exons are also spliced,
some aa are also lost, so protein is now shorter.
processing normally vs w progeria
normal
there is lamin protein
a lipid molec is added to C terminal
= farnesylation
2. methylation
3. cut = protein loses the added lipid molecule
w progeria
about 50 aa are deleted including the signal on where to cut
so when the lipid is added
and methylation happens
the signal for the cut, to lose the lipid is missing
lipid stays in strucutre
problem = instead of indv proteins int w e/o, they stick to mb = become lipid linked proteins
- nuclear envelope loses shape/activity( like gene repair) = mutation accumulate
cell can’t function, tissues can’t fn, deathd
different type of mutations, what it is
silent mutations = a nucleotide was changes but bc of redundancy of genetic code, same aa was coded for, neutral
missesne = nucleotide was changed, new aa , diff structure, diff fn
nonsense = nucleotide was changeed = new codon in stop codon. stops translation
loss of stop = nucleotide was changes = stop codon became an aa
frameshift = 1 base added/removed = the reading frame changes, everything is ruined from that point on.
consequences of each mutaton
silent = nothing
missense = if new aa is similar = not a problem
but for ex. if new aa can’t be phos, but old needed to be, = problem
nonsense= if early : big problem (short protein) non functional
if later = some fn could be perserved
loss of stop = addition of more aa than needed
if size is imp = big problem,
if not, = prolly not too bad
frameshift= if early; becomes completely diff protein = big problem
if end = might not be imp
loss/gain of function mutations
loss of function = codes for a nonfunctional protein
gain of function = codes for a protein w a new function
Loss = Need 2 copies of those mutation to completely lose the function inside the cells
Gain = Just 1 allele with that mutation is enough to get new function is enough
mutations occurring during DNA rep
bases could be misfired ,, but DNA poly has proof reading ability
if uncorrected could lead to permanent mutations in the next round of DNA rep.
in DNA rep each strand is a template.
one strand = all is good
other strand = put AG tog. = mismatch
if not watched, second round of DNA rep,
all good
one strand = AT
2 strand = CG
but now, instead of having GC in 2 daughter molecs like parents,
we have one right base pair and one wrong = mutation in 2nd
if DNA poly doesn’t catch mistake, all is lost?
no, there is a mismatch repair mechanism that also scans for errors
(look for mismatch = easy to find bc bases aren’t properly paired)
reco the mismatch and removes the wrong base, puts right one.
now, higher accuracy
mutations can occur spontaneously by ___ and ____, 2nd source mutations
why dangerous
depurination and deamination
depreciation = a nucleotide loses its base = becomes abasic (happens to G A)
deamination = C loses amino group, O takes place, becomes U
deprivation = problematic
of nucleotide has lost its base = dna rep happens, but when DNA poly sees no base, it doesn’t know what to do and moves on = frameshift error
deamination = problematic
C becomes U, C was binding G, U can’t bind G, if rep happens w/o repair, we get one pair GC, and other UA
modified base examples
oxidation, deprivation, deamination
BER- base excision repair mechanism
removes modified bases
steps
1. reco of modified bases
2. excision of the modified bases
3. removal of the same nucleotide
4. add missing nucleotide
5. ligase binds 2 adj nucleotides
UV induced mutations
UV damages DNA, covalently links 2 adjacent nucleotides with T bases
2 adj T nucletifes usually make H bonds not covalent bonds
usually linked by sugars not bases
problem = bc when DNA rep happens, DNA poly doesn’t know what to do with a T dimer, gets stuck/stops, DNA will break = damage to DNA
repairing a Thymine dimer
prepared by a nucleotide excision repair (NER) mechanism
reco of T dumers (proteins reco the covalent bond, bends the DNA sp cell knows which is the damaged cell
excision of damaged strand
DNA poly replaces gap
ligase binds together
radiation induced mutations
x rays cause single and double stranded breaks in DNA,
bc of their higher energy radiation,
instead of linking two T’s, they break strands of DNA
if left and not repaired quick, chromosomes rearrangement happens and may lose parts of chromosomes
chromosomal rearrangements
deletion of a chromosome segment
duplication 2 homologous chromosomes break at diff points, one chromosomes loses CD segments, other now has 2 CD segments, for ex.
inversion
2 cuts at either side of CDE, gets puts back but in EDC order
Reciprocal translocation
non homologous chromosomes change segments. now info of chromosome 5 is next to info of chromosome 2
repair of double strand DNA breaks , 2 types
non homologous
sloppy repair after break
just take 2 ends of molecs nad link using ligase,
we could lose DNA, could link 2 diff segments that shouldn’t have been linked
homologous
more proper, we don’t lose anything
lets say, we have 1 chromosome w 2 strands broken, in this situation, the homologous chromosome is near.
used as a template
mutations induced by chemical reagents
alkylating agents
add methyl and ethyl groups to bases, bind 2 strands of DNA covalently together, binds 2 bases together, makes DNA poly make mistakes, breaks DNA/damages it
Proflavin inserts itself bn bases of one strand, makes DNA poly confused, doesn’t know how to rep this strand = frameshift mutation.
