BCH5413 EXAM 4
Central Dogma of Molecular Biology DNA -> RNA -> Protein
endogenous factors that cause DNA damage error in replication
bully addict formation
oxidation
alkylation
hydrolysis
exogenous factors that cause DNA damage UV, chemicals, x-rays, ionizing radiation
emethanesulfate (EMS) DNA alkylation medicine for cancer
GC base pairing when guanine is exposed to EMS guanine to 06-ethylguanine and bins to thymine
EMS as a cancer treatment interferes with transcriptional and DNA replication
alkylation event that does not change base pairing attacks phosphodiester bond
endogenous sources of oxidative stress respiration, stress
exogenous sources of oxidative stress smoking, alcohol, pollution, water, pesticides, medications, food (meat)
Result of oxidative damage guanine oxidation
-biomarker of oxidative stress
-mutagenic
Hoogsteen base pairing - Occurs when one base is in the syn conformation.
-G-A base pair
UV-A damage free radicals
UV-B damage pyrimidine dimers
Gamma and X-ray damage ss or ds DNA break, altered bases (oxidized)
, BCH5413 EXAM 4
ionizing radiation radiation w/enough energy to free electrons from atoms forming ions, may
cause cancer (ex. gamma, X-rays, UV). Ionizes molecules around DNA ( water)
to form highly reactive free radicals that attack DNA backbone
oxidative stress, alkylating agents effect on DNA Base modification: alkylation, methylation, oxidation
polycyclic aromatic hydrocarbons effect on DNA adduct intercalation between bases
spontaneous events effect on DNA depyrimidation, depurination, backbone modification, base modifications
ionizing radiation effect on DNA ds break
environmental toxins effect on DNA ss break, DNA-protein crosslink
UV light effect on DNA photoproduct, thymidine dimers
chemo effect on DNA DNA-DNA crosslink
How does proofreading work? when a mismatched pair is recognized, respositions 3' terminus into other
catalytic site with the 3' to 5' exonuclease site is
removes mismatch
moves 3' back to polymerase site
mistake is corrected
MMR fixes which replication errors? base mismatches, loops, indels
MutH cleaves the unmethylated strand.( de novo)
Human MMR gene mutations associated with HNPCC? MSH2 and MLH1
microsatelite A short, specific and repeating sequence of nucleotides.
MMR and microsatellite instability not repetitive because new bases.
Base Excision Repair (BER) A DNA repair pathway that involves excision of a damaged base by DNA
glycosylase, followed by cleavage of the DNA backbone adjacent to the site
by an AP endonuclease. Nick translation, DNA polymerization, and ligation
complete the repair.
Nucleotide Excision Repair (NER) Repairs bulky lesions that alter/distort double helix
Central Dogma of Molecular Biology DNA -> RNA -> Protein
endogenous factors that cause DNA damage error in replication
bully addict formation
oxidation
alkylation
hydrolysis
exogenous factors that cause DNA damage UV, chemicals, x-rays, ionizing radiation
emethanesulfate (EMS) DNA alkylation medicine for cancer
GC base pairing when guanine is exposed to EMS guanine to 06-ethylguanine and bins to thymine
EMS as a cancer treatment interferes with transcriptional and DNA replication
alkylation event that does not change base pairing attacks phosphodiester bond
endogenous sources of oxidative stress respiration, stress
exogenous sources of oxidative stress smoking, alcohol, pollution, water, pesticides, medications, food (meat)
Result of oxidative damage guanine oxidation
-biomarker of oxidative stress
-mutagenic
Hoogsteen base pairing - Occurs when one base is in the syn conformation.
-G-A base pair
UV-A damage free radicals
UV-B damage pyrimidine dimers
Gamma and X-ray damage ss or ds DNA break, altered bases (oxidized)
, BCH5413 EXAM 4
ionizing radiation radiation w/enough energy to free electrons from atoms forming ions, may
cause cancer (ex. gamma, X-rays, UV). Ionizes molecules around DNA ( water)
to form highly reactive free radicals that attack DNA backbone
oxidative stress, alkylating agents effect on DNA Base modification: alkylation, methylation, oxidation
polycyclic aromatic hydrocarbons effect on DNA adduct intercalation between bases
spontaneous events effect on DNA depyrimidation, depurination, backbone modification, base modifications
ionizing radiation effect on DNA ds break
environmental toxins effect on DNA ss break, DNA-protein crosslink
UV light effect on DNA photoproduct, thymidine dimers
chemo effect on DNA DNA-DNA crosslink
How does proofreading work? when a mismatched pair is recognized, respositions 3' terminus into other
catalytic site with the 3' to 5' exonuclease site is
removes mismatch
moves 3' back to polymerase site
mistake is corrected
MMR fixes which replication errors? base mismatches, loops, indels
MutH cleaves the unmethylated strand.( de novo)
Human MMR gene mutations associated with HNPCC? MSH2 and MLH1
microsatelite A short, specific and repeating sequence of nucleotides.
MMR and microsatellite instability not repetitive because new bases.
Base Excision Repair (BER) A DNA repair pathway that involves excision of a damaged base by DNA
glycosylase, followed by cleavage of the DNA backbone adjacent to the site
by an AP endonuclease. Nick translation, DNA polymerization, and ligation
complete the repair.
Nucleotide Excision Repair (NER) Repairs bulky lesions that alter/distort double helix
