DNA Repair Mechanisms and Their Biological Implications in Mammalian Cells

This volume contains edited contributions from the speakers at the NATO Advanced Research Workshop on "DNA Repair Mechanisms and Their Biological Implications in Mammalian Cells" held October 1-6, 1988, at the Abbaye Royale de Fontevraud, Fontevraud France. The meeting was dedicated to Paul Howard-Flanders (Yale University, New Haven, CT. , 1919-1988), whose seminal con­ tributions to the DNA repair field include the cO-discovery of the excision repair pathway, the elucidation of post-repli­ cation repair in E. coli, the isolation of the lexA and recC mutants, and his extensive work on the enzymology of RecA. A plethora of recent developments in DNA repair mechan­ isms and related processes in mammalian cells have advanced our understanding of this field in a number of different areas and have given new emphasis to the ways these systems both resemble DNA repair processes in other groups of organisms in some respects yet are strikingly different from them in others. Within the past decade there have been a number of international conferences on DNA damage and repair mechanisms but none has been focused on these processes in mammalian cells.

Inhalt

Repair of Alkylation Damage in DNA.- Structure-Function Relationships in Alkylation Damage and Repair.- The Roles of Beta- and Delta-Elimination in the Repair of AP Sites in DNA.- Imidazole Ring-Opened Purines: Occurence and Repair in Escherichia coli and Mammalian Cells.- Substrate Specificity of the Formamidopyrimidine-DNA Glycosylase of E. coli: Repair of the Imidazole Ring-Opened Form of N-Hydroxy-2-Amino-Fluorene-Guanine Adducts in DNA.- Investigation of Sequence Specificity in DNA Alkylation and Repair Using Oligodeoxynucleotide Substrates.- Towards a Role for Promutagenic Lesions in Carcinogenesis.- Acquisition of Resistance to Alkylating Agents by Expression of Methyltransferase Gene in Repair-Deficient Human Cells.- The Mer Minus Phenotype, Patient Response to Nitrosoureas, and Protooncogene Activation in Human Glioblastomas.- The Molecular Basis of Alkylating Agent Resistance in Mammalian Cells.- Differential Repair of O4-Methylthymine and O6-Methylguanine in Rat and Hamster Liver.- Formation of 1, N6-Ethenodeoxyadenosine and 3, N4-Ethenodeoxycytidine in DNA from Several Organs of Rats Exposed to Vinyl Chloride.- The Role of O6-Alkylguanine in Cell Killing and Sister Chromatid Exchange Induced by Alkylating Agents.- Inducible Responses to DNA Damage.- Inducible Repair in Mammalian Cells Treated with Alkylating Agents.- An Update of the Mammalian UV Response: Gene Regulation and Induction of a Protective Function.- DNA Repair Related Events.- The Transportation of AP Endonuclease from Cytoplasm to Nucleus in Mammalian Cells.- DNA Damage and Oxygen Species.- Mutagenesis.- Molecular Studies of Mutagenesis using Plasmid Vectors in Xeroderma Pigmentosum Cells.- Molecular Analysis of Mutations at the HPRT Locus: UV Mutation Spectra in Normal and UV-Sensitive V79 Chinese Hamster Cells.- Comparison of the Mutational Specificities Exhibited by BPDE in Escherichia coli and CHO Cells.- Deoxyribonucleotide Pools, DNA Repair and Mutagenesis.- Recombination and Mismatch Repair.- Duplex-Duplex Homologous Recombination Catalysed by a Human Nuclear Extract. Involvement in Double-Strand Break Repair.- Proteins from Yeast and Human Cells Specific for Model Holliday Junctions in DNA.- Characterization of a Strand Transferase Activity from Human Cells.- Mismatch Repair in Mammalian Cells: Approaches to the In Vitro Study of DNA Mismatch Correction Reactions.- Mismatch Repair Patterns in Simian Cells Correlate with the Specificity of a Mismatch Binding Protein Isolated from Simian and HeLa Cells.- Chromatin Proteins and Chromatin Structure in DNA Repair.- DNA Excision Repair at the Nucleosome Level of Chromatin.- Modulation of Activity of Human Chromatin-Associated Endonucleases on Damaged DNA by Nucleosome Structure.- Relationship Between DNA Repair and Transcription in Defined DNA Sequences in Mammalian Cells.- Non-Random Distribution of UV-Induced Repair in Higher-Order Chromatin Loops in Human Cells and its Relationship to Preferential Repair of Active Genes.- Electron Microscopic Visualization of Chromatin Structure at Sites of DNA Excision Repair Following Ultraviolet Irradiation of Cultured Human Fibroblasts.- Poly(ADP-Ribosyl)ation Reactions and Modulation of Chromatin Structure.- Variation of Nuclear ADP-Ribosyl Transferase in Rat Liver Carcinogenesis and in Synchronized HeLa Cells.- DNA Repair Processes in Mutant Cells Deficient in Poly(ADP-Ribose) Synthesis.- Repair Defective Cell Types.- Co-Recessive Inheritance: A Model for Diseases Associated with Defective DNA Repair.- Mammalian DNA Ligases and the Molecular Defect in Bloom's Syndrome.- Detection of Unique Antigenic Lesions in the Uracil DNA Glycosylase from Bloom's Syndrome.- DNA Ligase Activity in Human Cells from Normal Donors and from Patients with Bloom's Syndrome and Fanconi's Anemia.- Processing of Photoinduced Cross-Links and Monoadducts in Human Cell DNA: Genetic and Molecular Features.- Parallels Between Nucleotide Excision Repair in Human Cells and E. coli.- Mechanisms of Resistance to Ionising Radiations: Genetic and Molecular Studies on Ataxia-Telangiectasia and Related Radiation-Sensitive Mutants.- Defective DNA Synthesis and/or Repair in Amyotrophic Lateral Sclerosis.- Genetic Analysis in Trichothiodystrophy Repair Deficient Cells Confirms the Occurrence of Xeroderma Pigmentosum Group D Mutation in Unrelated Patients.- Chinese Hamster Cell Lines Defective in DNA Repair.- DNA Repair Genes and Oncogenes in DNA Repair.- Human DNA Repair and Recombination Genes.- Molecular Genetic Dissection of Mammalian Excision Repair.- The Cloning and Characterization of a Candidate Gene for the Correction of the Xeroderma D Defect.- Characterization of Chinese Hamster Ovary Cell Mutants Hypersensitive to DNA Damaging Agents.- Oncogene Activation in Xeroderma Pigmentosum Skin Tumors.- Anticancer Drugs in DNA Repair.- Heterogeneity in the O6-Alkylguanine DNA Alkyl-Transferase (AGT) Activity of Human Peripheral Blood Lymphocytes (PBL's).- Formation and Repair of Adducts that Lead to Cross-Links in DNA Treated with Chloro-Ethylating Agents.- Induction of Futile DNA Repair Processing by Bifunctional Intercalators.- Participants.- Author Index.