various ways in which dna damage leads to mutations in proteins insertion

Download Various ways in which DNA damage leads to mutations in proteins Insertion

Post on 03-Jan-2016




0 download

Embed Size (px)


  • Various ways in which DNA damage leads to mutations in proteinsInsertion

  • MutationGenetic Mutations leading to food productionCanola Cauliflower

  • CarcinogensCarcinogens agent that inducing mutation of DNA leading to cancerProcarcinogens are not carcinogens, 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 pyrimidines along one side cis-syn-cyclobutane pyrimidines dimersThymine or cytosine dimersFormation of dimer distorts base pairing structure=> effect replication and transcription

  • Pyridimine-pyrimidine(6-C4) photoproducts 25%3

  • Psoralen, intercalating agent photosensitizer w/ UV

  • DNA damageoxidative deamination: spontaneous reaction at 37oC

    Guanine Xantine

  • Reaction with alkylation agentsAddition of methyl group to bases S-adenosylmethionine some agents used in chemotherapy

  • CytosineThymineAlkylation agentAlkylation of guanineO6-methylguanine

  • BenzopyreneBenzopyrene Dihydrodiol epoxide

  • Reaction with ROS;Number of mutations increase with ageguanineDepurination 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 repair

    Variety 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 strandWhat 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

  • Xeroderma pigmentosum PD ,

  • Cockayne syndrome DNA ,