DNA Mutations and Repair Flashcards
Mutation
any heritable change in genetic material
Heritable
mutations passed through cell division
Somatic Cells
body cells. mutations that are somatic are passed only to the daughter cells in that area and are not transferred to future generations
Germ Cells
reproductive cells.
Mutations passed to offspring
Rates in mammals
Rate of mutation in somatic cells much higher than rate in germ cells
Mutational hotspots
certain nucleotides are prone to mutations
percent of human genome that encodes for proteins
Only 2.5%
So most mutations in noncoding DNA, so causes no changes (neutral)
mutation per organismal generation
Most important for germline mutations
important to evolutionary processes because through transmission between generations they may become present in many individuals.
mutation per cycle of DNA replication
Most important in somatic cells
A somatic mutation is not transmitted to future generations, but to progeny cells in mitotic divisions. Only the cells that descend from the
mutated cell are affected.
Higher mutation rates
RNA viruses and retroviruses
Lots of breakage and repair in lifecycle
somatic cells
Lower mutation rates
DNA molecules
multicellular organisms
Germline cells
• Mutation per organismal generation
o Accumulating mutations over genome in your life time
o # germline mutations, genome size
o youre passing on about 30 mutation to you offspring
• mutations that occurred in you before you passed them on
• But you didn’t have these mutations
• Mutation per cycle of DNA replication
o Linked to cancer
o Fidelity of replication process in any gene in your body
o (first one we looked at)
o Probability that mutation can occur at any nucleotide at any time
o There are certain types of “viruses” that have a very high mutation rate
• RNA viruses and retroviruses
o Multicellular organisms
• Much much much lower mutation rate
• Pretty good replication accuracy occurring
Male v Female
o Sperm production: rapid replication, MUCH higher replication rate than female eggs
o By the time you’re 30, germ line cells have 400X greater mutation rate (sperm cells specificially)
• Older fathers→ higher probability of autistic children
Multiple Mutation Model of Cancer Progression: Somatic Mutations
o Start with a colon cell
• Divides
• More dividing
• One cell line you get a mutation in APC
• Divides and passes on mutation to its “offspring”
• Cell line carring muated APC gene
• Eventually pick up a mutation in ras
• 2 mutation in cell line
• mucho much more dividing
• APC and ras mutation, give rise to more mutated cells
• Accumulate third mutation in TP53, go from benign to malignant.
Mismatch repair
enzymes can fix errors missed by DNA polymerase
• Proofreading done by DNA polymerase
• Last base added is checked and if incorrect, removed and replace with right base
Small Scale Mutations
- Synonymous (silent)
- Nonsynomouys (missense)
- Nonsense muatations
Large Scale Mutations
- Insertion
* Deletion
Point Mutations
o Incorrect base pair that isn’t caught
o Inccorect base pair then correctly paired with new partner, so not seen as an error anymore because base pairing is now correct
o Original copy still around
Synonymous mutation
at amino acid level
When both original and mutated codon code for the same protein
Change at third position
Silent Mutation
At genomic level
When both original and mutated codon code for the same protein
Change at third position
Nonsynonymous mutation
amino acid level
• Most likely change at second position site in codon
• Changes what amino acid is coded for
o Will make different protein
Missence Mutation
genomic level
• Most likely change at second position site in codon
• Changes what amino acid is coded for
o Will make different protein
Nonsense mutations
• Change in first position site • Incorporation of stop codon instead of protein coding • Shortened protein codon • Depends on where in protein it occurs o Can totally shut down synth of protein
Sickle Cell Anemia
o Altered form of beta subunit of hemoglobin
o Don’t allow red blood cells to effectively carry oxygen
o Sickeled shape instead of round
Deletions
o Delete one amino acid (1 codon)
• Cystic fibrosis
• Code for one less protein, missing entire codon that encodes for it
• Result: incorrectly folded protein
• Misfolded gotten rid of by cell
• Without it, cant regulate amount Cl passing in and out of cell and maintaining correct concs on same side of cell
• Abnormal secretions in lungs, liver, pancreas and other glands
Frame Shift Mutation
o Insertion or deletion of one or two bases results in disruption/shifting of reading frame
o Change all amino acids encoded there
o Encode totatally different proteins
Transposable Elements are…
DNA sequences that can move from one location to another in genome
• Can be inserted into protein coding gene, causes huge frameshift
o Can disrupt function of entire gene
• When removed, function of original gene can be restored
• Discovery: Barbara McClintock and corn
o Transposable element move into anthocyanin, change pigmentation
Xeroderma Pigmentosum
o XP: rare autosomal recessive disease in humans: development of skin lesions
• Caused by mutations of one of several nucleotide excision repair systems.
• These mutations mean the cells of peple with XP cant repair DNA damaged by UV radiation (sun xposure)
Due to errors in repair mechanisms
Nucleotide Exision repair
• Can remove more than one damaged base • Mismatching of bases • Damaged bases • Like damge to backbone Removes a STRAND of DNA.
Base Exision repair
• Uracil
• Uracil glyclosolase cleaves out U, leaves deoxyribose backbone
• Endonucleouse IDs where there is bulge where base was removed. Removes portion of backbone
• Sews back together
remove a SINGE BASE
DNA ligase
seal breaks in backbone
Mismatch repair
single mis-paired bases repaired by removing and replacing DNA segment • Incorrect pair • Enzyme makes a break • Enzyme chews up strand • Enzyme to re make the strand
How mutations arise
o Spontaneously
o Mutagens
Mutagens
- E-rays: breaks in backbone
- UV light: thimine dimers make kinks in DNA
- Bleach or H2O2 causes loss of base, cap
- Smoking can add weird side groups=improper pairing
Balitimore thing
all has to pass from whatever genetic material comes in through mRNA so it can make protein using the host cell
need positive mRNA strand
Polio/Dengue
come in as + single strand RNA
make - stranded RNA, so we have double stranded RNA, can make proteins more easily
Flu
single stranded RNA -
Make RNA + using RNA depended RNA pol
can then encode proteins
another + RNA strand
copy using reverse transcriptase, make - DNA and + DNA, makes double stranded DNA, replicate, make mRNA
Dideoxide
Hydrogen where it should have hydroxyl
strand cant grow, terminates
Cystic Fibrosis
abnormal secretion in lungs, pancreas, liver
missing phenoalenine (missing entire codon and genome level)
Incorrectly folded protein
discarded
the AFCR gene regulates Cl ion levels
shorter life span
Duplication and Divergence
Globin
Duplicate, diverge allows them to be retained in genome
ancestral copy–> 2 decendents
gene family that arose millions of years ago
Inversion
Double strand break
during repair, inserted in opposite direction (inverted)
Recipricoal Translocation
Large change chromosome break in DNA repair sews it together wrong resulting chromosomes that are part of ancestor of each version (fusion) join nonhomologus sections
X-rays
breaks in sugar phosphate backbone
UV Light
Thymine dimers
kinks in DNA
Bleach, H2O2
gaps
deltion of bases
Smoking
add weird side groups to bases
improper pairing
