Radiation damage to cellular DNA, caused by ultraviolet (UV) light, has a number of component processes. One of these is cross-linking of chromosomal proteins to DNA. The present proposal emphasizes this aspect of UV radiation damage to eukaryotic chromatin. The long term objective of our research program in this area is to elucidate the chemical nature of nucleic acid-protein photocross-linking and to assess quantitatively the importance of individual nucleobase-amino acid mixed products, as a function of UV dose, to the total cross-linking of proteins of DNA in eukaryotic chromatin. The present research proposal has specific goals of trying to answer the following questions: which nucleobases and amino acids participate in the photocross-linking of histones to DNA in chromatosomes (one of the basic structural units of eukaryotic chromatin)? What are the quantitative yields, as a function of UV dose, of those mixed products that are important as contributors to the photocross-linking? The following approach will be used to answer these questions. A set of nucleobase-amino acid (or nucleoside-amino acid) mixed products will be prepared by routes involving reaction of the nucleobase or nucleoside with amino acid or appropriate amino acid derivative. The resulting mixed products will be characterized as to their chemical, chromatographic and spectroscopic properties. Using this information, they will be sought in hydrosylates of UV-irradiated chromatosomes. Quantitation of mixed products will be done through the use of chemically derivatized hydrosylates of photocross-linked chromatosomes, in conjunction with high performance liquid chromatography and chemically derivatized standards of known mixed product concentration.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM023526-11
Application #
3271686
Study Section
Radiation Study Section (RAD)
Project Start
1977-04-01
Project End
1992-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
11
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Pharmacy
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Shetlar, Martin D; Hom, Kellie; Venditto, Vincent J (2013) Photohydrate-mediated reactions of uridine, 2'-deoxyuridine and 2'-deoxycytidine with amines at near neutral pH. Photochem Photobiol 89:869-77
Hom, K; Strahan, G; Shetlar, M D (2000) Ring opening photoreactions of cytosine and uracil with ethylamine. Photochem Photobiol 71:243-53
Shaw, A A; Wainschel, L A; Shetlar, M D (1992) The photochemistry of p-aminobenzoic acid. Photochem Photobiol 55:647-56
Celewicz, L; Shetlar, M D (1992) The photochemistry of 5-methylcytosine and 5-methyl-2'-deoxycytidine in aqueous solution. Photochem Photobiol 55:823-30
Shaw, A A; Falick, A M; Shetlar, M D (1992) Photoreactions of thymine and thymidine with N-acetyltyrosine. Biochemistry 31:10976-83
Shaw, A A; Wainschel, L A; Shetlar, M D (1992) Photoaddition of p-aminobenzoic acid to thymine and thymidine. Photochem Photobiol 55:657-63
Shetlar, M D; Rose, R B; Hom, K et al. (1991) Ring opening photoreactions of 5-bromouracil and 5-bromo-2'-deoxyuridine with selected alkylamines. Photochem Photobiol 53:595-609
Shaw, A A; Shetlar, M D (1989) The photochemistry of 2-alkoxycytosines in phosphate buffer and its link to cytosine photochemistry in alcoholic solution. Photochem Photobiol 49:273-7
Shaw, A A; Shetlar, M D (1989) Ring-opening photoreactions of cytosine and 5-methylcytosine with aliphatic alcohols. Photochem Photobiol 49:267-71
Shetlar, M D; Hom, K; Distefano, S et al. (1988) Photochemical reactions of cytosine and 5-methylcytosine with methylamine and n-butylamine. Photochem Photobiol 47:779-86

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