Mutagenesis is a part of genetics involving variations in genetic information that are produced by abnormal molecular trauma but are carried there after by normal genetic means. Mutagenesis research is relevant to cancer, where atypical cell development is thought to depend on alterations of the genotype. Basic mutagenesis research also may reveal fundamental DNA-Associated functions that can influence genetic stability, which is important in immunology and developmental biology. This proposal continues a study of certain damages-induced functions at particular sites in template DNA. The roles of excision repair and recovery DNA synthesis in ultraviolet mutagenesis of E. Coli at targeting sites insensitive to photoenzymatic reversal (PR) is used as a tool to selectively remove a class of DNA damage and thereby to test specific associations. Individual categories of mutation are distinguished that indicate specific base substitutions. Therefore the frequencies of certain mutations are used as a measure of relative repair and/or fixation of an altered DNA sequence at specific targeting damage. Mutagenesis in a glutamine tRNA gene (suppressor mutations or forward inactivating mutations) expressed in two types of DNA sequence will be compared to learn whether the mode of gene expression affects targeted mutagenesis. Mutation frequency decline, which previously was shown to affect a particular lesion sin the transcribed DNA strand, will be examined with the assay for forward mutations to be measured with the assay for forward mutations to measure effects throughout, the glutamine tRNA gene. Repair of pyrimidine diners in either DNA strand of the glutamine tRNA gene will be measured biochemically for comparison with the mutation date. Mutational DNA synthesis (incorporates the altered DNA sequence) will be delineated by using the effect of DNA photolyase bound to a targeting dimer, which blocks mutagenesis, to mark the relevant synthesis. And the recovery of DNA synthesis after PR will be studied to find a correct explanation for delayed PR mutagenesis processes from the initiating DNA lesions, through the intervening activities and/or influences of gene structure - function, to the ultimate altered DNA sequences.
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