ccch 7 Flashcards
Mutation
changes in the nucleotide sequence of DNA
spontaneous mutation
natural, rep errors, reactive oxygen from metabolism
induced mutation
any chemical or physical agent that causes hella mutations
mutations importance
- genetic variation
- advantage consequences
- important tools for understanding genes
point mutations
single nucleotide alterations, (nucleotide substitution)
bigger mutations
trinuclotide repeats, insertions, deletions, chromo rearrangement
mutation hotspot
places that are more likely to mutate
transition mutation
pyrimidine/purine replace with like
transversion
purine replace with pyrimidine, or vise versa
post mutations become permanent if
its replicate into a DNA sequence (not repaired)
types of mutations
silent mutation, missense mutation, nonsense mutation
missense mutation
amino acid swapped for another
nonsense mutaiton
amino acid to stop codon
sickle cell is caused by
missense mutation, A to T (tranvsersion)
insertions and deletions
leads to adding/subtraction amino acids, frameshift
cystic fibrosis is caused by
deletion mutation, CFTR cannel mutation
frame shift
insertion or deletion causing the shift in a frame, usually harmful
RTH thyroid hormone sensitivity
caused by frameshift, goiter, abnormal psychology
mutation need to be in - to have an effect
gene coding region or area important to it, needs to not be silent
trinucelotide repeats, most common
CGG, CAG, GAA
usually make triple helix, neurological disorders
fragile x and Huntingtons is caused by
trinucleotide repeats
repeats caused by
unequal cross over, slipping during DNA replication
unequal crossing over
one is short and other is longer
slipping durring DNA rep
forms a slipped structure during replication
mutagen DNA damage
single base changes, structural distortion , DNA backbone damage
single base changes cause (what types of mutations)
single base conversion, alkylation, oxidation, minor effect of structure
deamination
mutagenic single base change, most frequent, hydrolytic, C to U is common
alkylation
adds methyl groups, nitrosamines
GC to AT
oxidation
gains oxygen bond, radiation
GC to TA
structural distortion
UV radiation causes Tymine dimers, creates backbone bulge and fucks everything up
DNA adduct (structural)
DNA binds to cancer causing things, structural distortion caused by intercalating agents and base analogs
ethidium bromide (structural)
carcinogen, intercalating agent, insert bn DNA bases
5 bromouracil (structural)
thymine analogue, mispair with guanine
Formation of abasic site
backbone damage, loss of base from nucleotide
dsDNA break
worst, ionizing radiation and chem compounds causes this
cellular responses to DNA damage
Damage bypass, damage reversal, damage removal and replacement
translation synthesis
allows bypass damage (t-t) with error prone polymerases,
Error pro DNA poly provides
trade off bn death or high mutation rate
polymerase switching
replacement of high fidelity poly for a low error prone one to bypass damaged DNA
DNA poly eta
translesin synthesis past TT dimer by inserting AA, has extra wide active site
prokaryote lesion Bypass needs the
SOS response
direct repair
correct dna damage with specific steps
pro of direct repairs
specific damage repaired accurately
con of direct repair
bad from evolutionary standpoint, needs specific enzyme
direct reversal examples
DNA photolyase, dna methyltransferase, SPRTN
DNA photolyase
uses UV from blue light break the covalent bonds holding two pyrimidines
dna methyltransferase
takes the methyl group and moves it
SPRTN protease
removes DNA protein cross links during synthesis, controlled by ubiquitin
single base change repair
base excision repair, mismatch repair
structural distortion repair
nucleotide excision repair
base excision repair requires
requires DNA glycosylases (cuts base off sugar), leaves a basic cite, can be short patch or long patch
short patch repair
lyase cuts strand on 3’ end, APE1 removes the phosphoriboes, poly adds new nucleotide, ligase seals backbone
long patch repair
APE1 cuts strand form 5’ end, poly delta or eta displaces a short old strand and synthesizes new dna, FEN1clips flap of DNA, ligase seals backbone
mismatch repair
errors during replication, removes larges section of DNA, repairs polymerase errors, MUT proteins
nucleotide excision repair
longer structural distortion repair
ex t-t dimer
can cut up to 30 nucleotides
XP proteins
xp protiens
human nucleotide excision repair portein
global genome repair
ids lesions in the whole genome
transcription coupled repair
ids lesion in the transcribed strand of active genes
nucleotide excision repair subtypes
global genome and transcription coupled
xeroderma pigmentosum
mutations in the nucleotide excision repair proteins
sensitive to the sun
restive mutation
double stranded DNA breaks repair mechs
homologous recombinant repair (accurate)
non homologous end joining (not as accurate)
homologous recombinationand what complex is used for it
gets genetic info form an undamaged homo chromosome, MRN complex
nonhomo end joining
direct ligation of ends all willy nilly
doesn’t have to be from same chromie
huge trade off to take care of lethal breaks,
XU protein 70/80
heteroduplex DNA
duplex DNA formed during recombination composed of single DNA strands originally form different homologs
Holliday Junction
recombination intermediate where 2 recombining duplex are joined covalently by single strand crossovers
resolvsome
resolved Holliday junctions
nonhomo end joining leads too
mutations
nonhomo end joining proteins
KU 70/80 dimers, recognize the ends
germ line mutations unrepaird
(germ cells) passed to next generation
natural selection
somatic mutations unrepaired
not transmitted, may lead to cancer, can effect survival rate
sanger sequencing
synthesize complementary DNA in vitro with Nucleotide homologues that terminate the chain
translation synthesis proteins
DNA poly IV and V (bacteria),
DNA polymerase eta, humans
MSH protein
recognized damage in 5’ excision of mismatch repair
MLH/PMS protein
endonuclease activity, activates at PCNA, 3’ excision, mismatch repair
BRCA 1, BRCA 2
dsDNA recombin proteins
