topic 6 Flashcards
(26 cards)
what is DNA damage
any modification of DNA that changes its coding properties or normal function in transcription or translation
What are the 3 types of changes in DNA
- gene mutation
- recombination
- transposable elements
list the 7 types of chemical modifications for DNA
- deamination
- base loss by depurination /depyrimidination
- oxidation – electron loss
- alkylation
- nitrous acid-induced DNA damage
- energy-rich radiations cause inter-base, inter-strand c
crosslinkings, and strand breaks - action of intercalating agents
- other chemical mutagens, ie. base analogs
result of point mutations
missense, nonsense mutations
result of a frameshift mutation (new vs old strand)
- slippage of template → deletion
- slippage of new strand → addition
what does the enol form of Thymine pair with?
how does this alter the DNA sequence?
keto form of Guanine
T:A → eT:G → C:G
what does the enol form of Guanine pair with?
how does this impact the DNA sequence?
keto form of Thymine
G:C → eG:T → A:T
what does the imino form of Adenine pair with?
how does this impact the DNA sequence?
amino form of Cytosine
A:T → iA:C → G:C
what does the imino form of Cytosine pair with?
how does this impact the DNA sequence?
amino form of Adenine
C:G → iC:A → T:A
What does base pairing of tautomeric forms of bases result in?
transitions or transversions
What is a transition mutation?
exchange of purine-pyrimidine base pair for the other purine-pyrimidine base pair
- C::G -> T::A or T::A -> C::G
What is a transversion mutation?
exchange of purine-pyrimidin
base pair with a pyrimidine-
purine base pair or vice versa
- C::G -> G::C or A::T
What are the 2 steps of Substitution Point Mutation?
- incorrect nucleotide incorporated by DNA pol during replication (mismatching)
- mismatched based not repaired and is replicated (mutation)
Cause of indels
aberrant DNA recombination or DNA polymerase slippage during replication
how can the number of triplet repeats in fragile X locus be determined
length analysis of PCR products
- additional repeats creates longer segments
how do alkylating agents chemically damage DNA?
electrophilic attack of the DNA backbone
What type of reaction damages nucleotides and the phosphodiester backbone?
hydrolytic reactions with H2O
Which bases can undergo deamination and what to they transform into?
– Cytosine → Uracil
– Adenine → Hypoxathine
– Guanine → Xanthine
– 5-Me-Cytosine → Thymine
THYMINE CANNOT BE DEAMINATED
What do Hypoxathine and Xanthine base pair with?
Cytosine - can pair with, may also continue with their normal base
What bond does hydrolytic reactions cleave?
What does this create?
- cleaves the glycosyl bond between the nitrogenous base and the deoxyribose
- creates an abasic (AP) site (aka apurinic or apyrimidinic site)
what can depurination/ depyrimidination result in?
base loss or base-pair
transition
Where might strand break and bass loss occur in deoxyribose?
Abasic Site
What produces ROS? what is 1 function of ROS?
Reactive Oxygen Species (ROS)
- cellular metabolism, (cellular respiration in mitochondria,
detoxification in the liver, ionizing radiation)
- can function as DNA-damage reagents
ROS reactions
oxidize:
thymine -> thymine glycol
guanine -> 8-oxo-guanine
