BIO 205 DNA MUTATION AND REPAIR Flashcards
sources of DNA damage
- spontaneous (self-generated)
2. environmental
SPONTANEOUS DAMAGE
- hydrolytic attack
- oxidative attack
- replication error
what is hydrolytic attack
common food preservatives & processed foods (nitrates, nitrites)
what is oxidative attack
breaks down DNA backbone
ENVIRONMENTAL DAMAGE
- chemical exposure
- ionizing radiation
- UV exposure
- vaping
examples of chemical exposure
tobacco, food chemicals, pollutants, chemotherapeutics
examples of ionizing radiation
x-ray, gamma-ray
UVA versus UVB
UVA burns skin
UVB burns DNA (2-10% reaches basal layer)
DNA damage can lead to ___
mutations
which DNA damage is passed on through generations
germ line
two types of DNA damage
- germ line
* somatic
germ line mutation example
sickle cell anemia
• genetic disease
• inherited blood disorder
what is sickle cell anemia
single nucleotide change (A to T)
somatic mutation
- CANNOT BE PASSED
- proliferating cancer cells
- changes of getting cancer = age correlated
- cannot be passed
types of DNA mutations
point mutation, deleting, insertion, frameshift
point mutation also called ____
single base substitution
which DNA mutation is most common
single-base sub. / point mutation
point mutation
one letter change
deletion
base is removed from the DNA sequence
insertion
base is inserted into the DNA sequence
deletion/insertion not drastic when ____
in multiples of 3
In insertion or deletion can cause a ________
frameshift mutation
large scale damage: The four types of chromosomal mutations
deletions, duplications, inversions, translocations
codons are always __ base-pairs (nucleotides) in length
3
frame shift mutation
every nucleotide changed from error — continuing
example of large scale damage
chromosome 9 and 22 SWITCH • chrom 9 derivative
• Philedelphia chrom
• Fusion product is uncontrolled
• BCR/ABL Gene fusion
results in CML (chronic myeloid leukemia)
DNA alterations leading to mutations
- Damage by water
- Deamination
- Depurination
- UV radiation
- High energy radiation
DNA alterations: damage by water
cleavage by addition of H2O
(hydrolysis) - leads to loss of purine
DNA alterations: deamination
- hydrolysis reaction of C to T/U
* substation of one base pair for another
DNA alterations: depurination
missing A or G (nothing to pair with)
• remove pair (frame shift)
• or replace unpaired
steps in DNA repair systems
search, recognize, excision
types of DNA repair systems
- mismatch excision repair
- nucleotide excision repair
- base excision repair
- double-strand break repair
what DNA Polymerase is responsible for repair in eukaryotes
polymerase II
MISMATCH REPAIR (MMR) summary
• base mismatches or small insertion/deletion loops
how does mismatch repair work in E. COLI
- mut S recognizes mismatch on nonmethylated daughter strand (temporarily unmethlyated after replication)
- mut L binds to mut S
- L activates H, which cleaves the unmethylated strand opposite site of methylation
- S and L (with helicase - keeps strands separated - and exonuclease) cut out mismatched portion
- gap filled by polymerase III, sealed by ligase
how to know what is parent strand?
new strand?
- parental is methylated
* daughter strand is TEMPORARILY unmethylated after replication
what does mismatch repair involve in E. COLI
mut S, mut L, mut H proteins
mechanism of DNA mismatch repair in eukaryotes
newly synthesized
strand and template strand difference UNKNOWN
- new strand has nicks
defects in mismatch repair mechanisms in eukaryotes lead to
hereditary colon cancer in humans
nucleotide excision repair needed for DNA damaged by __
UV radiation
harmful UV radiation effects… thymine dimer :
- 2 adjacent thymine bases become covalently bonded to one another - form THYMINE dimer
- creates a kink in the DNA that blocks the progression DNA polymerase
- If unrepaired, polymerase skips over the dimer, resulting in a small deletion
Nucleotide Excision Repair (NER) used for
repairing thymine dimers and pyrimidine dimers
- targets bulky lesions, removes DNA on either side
steps of nucleotide excision repair
- Recognition of abnormal dimers
- Excision of a segment (includes dimer)
- DNA Polymerase fills gap
- Gap sealed by DNA Ligase
Xeroderma pigmentosum caused by
UV radiation
- an inherited disease that results from failure to repair pyrimidine (thymine) dimers
high energy radiation causes
single & double-stranded breaks in DNA (splitting a chromosome in two)
Xeroderma pigmentosum facts:
- extreme sensitivity to sunlight
- predisposition to skin cancer (8 y/o)
- recessive
hemimethylated
one strand methylated
