various ways in which dna damage leads to mutations in proteins insertion
TRANSCRIPT
Various ways in which DNA damage leads to mutations in proteins
Insertion
Mutation
Genetic Mutations leading to food production
Canola Cauliflower
• Carcinogens– Carcinogens – agent that inducing
mutation of DNA leading to cancer– Procarcinogens – are not carcinog
ens, but can be activated by metabolic processes
Ames testHis- strain of bacteria Salmonea tyrphimuriumHis- can not synthesize HisMutagenesis indicates reversion of strain to His+
Cells of S. tyrphimurium is spread on culture plate lacking his in the presence of tested mutagent, growing cells indicated reversion to His+ strain.
• UV, short wave length (254nm)– Covalently link adjacent pyri
midines along one side– cis-syn-cyclobutane pyrimidi
nes dimers– Thymine or cytosine dimers– Formation of dimer distorts b
ase pairing structure=> effect replication and transcription
Pyridimine-pyrimidine(6-C4) photoproducts
이량체의 25%3 시간 후 자동제거
Psoralen, intercalating agent photosensitizer w/ 장파장 UV
DNA damage• oxidative deamination: spontaneous reaction at 37oC
N
NN
N
O
NH2
H
H
N
NN
N
O
O
H
H
Guanine Xantine
Reaction with alkylation agents
-Addition of methyl group to bases- S-adenosylmethionine
- some agents used in chemotherapy
N
N
NN
O
NH2
HH
N
N
NN
O
NH2
H
CH3
Cytosine
Thymine
Alkylation agent
Alkylation of guanine
O6-methylguanine
Benzopyrene Benzopyrene Dihydrodiol epoxide
• Reaction with ROS;– Number of mutations increase with age
N
NN
N
O
NH2
H
Hguanine
Depurination – cleavage of glycosyl bond results into removal of base - abasic sites, apurinic sites
DNA glycosylases remove altered bases
• Deamination of cytosine, particularly 5-methyl cytosine leaves uracil (thymine if 5methyl cytosine) in the DNA. Uracil would pair as thymine during replication and thus cause a mutation. Uracil-N-glycosylase removes uracil from DNA. An endonuclease then cleaves the backbone at that site, creating a substrate for NER
• Nucleotide excision repairVariety of damages, includes pyrimidine dimers, chemotherapic agents as cis platine
Repair mechanism involves removal of several nucleotides
E. coli: UvrABC endonuclease complex
UvrA – recognize helix distortion UvrB – separation of DNA strands (helicase activityUvrC – catalyses dual cleavageUvrD – exonuclease activity removes oligonucleotidePol I fills the gapDNA ligase – couple the nick
Mismatch repair corrects the unmethylated strand
What happens if the “old” strand needs repair?eg 5-methyl cytosine>deamination to 5-methyl uracil (=thymine!). In E. coli a small fraction ofC is 5-methylated and these are “hot-spots” forspontaneous mutation. This implies that 5-methyl cytosine is frequently either not repaired or ismistakenly repaired on the “wrong” strand.
Mis-paired bases
색소건피증 Xeroderma pigmentosum
햇볕에 극도로 민감PD 절제회복의 결함 , 피부암으로 발전
Cockayne syndrome
전사가 빠른 유전자의 DNA 상해회복의 결손난장이 , 조로