Mechanisms Of Dna Damage Recognition 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.

Stands as the most comprehensive guide to the subject—covering every essential topic related to DNA damage identification and repair. Covering a wide array of topics from bacteria to human cells, this book summarizes recent developments in DNA damage repair and recognition while providing timely reviews on the molecular mechanisms employed by cells to distinguish between damaged and undamaged sites and stimulate the appropriate repair pathways. about the editors... WOLFRAM SIEDE is Associate Professor, Department of Cell Biology and Genetics, University of North Texas Health Science Center, Fort Worth. He received the Ph.D. degree (1986) from Johann Wolfgang Goethe University, Frankfurt Germany. YOKE WAH KOW is Professor, Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia. He received the Ph.D. degree (1981) from Brandeis University, Waltham, Massachusetts. PAUL W. DOETSCH is Professor, Departments of Biochemistry, Radiation Oncology, and Hematology and Oncology, and Associate Director for Basic Research, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia. He received the Ph.D. degree (1982) from Temple University School of Medicine, Philadelphia, Pennsylvania.

DNA Repair Mechanisms is an account of the proceedings at a major international conference on DNA Repair Mechanisms held at Keystone, Colorado on February 1978. The conference discusses through plenary sessions the overall standpoint of DNA repair. The papers presented and other important documents, such as short summaries by the workshop session conveners, comprise this book. The compilation describes the opposing views, those that agree and dispute about certain topic areas. This book, divided into 15 parts, is arranged according to the proceedings in the conference. The plenary sessions are grouped with the related workshop and poster manuscripts. The first two parts generally tackle repair in terms of its identification and quantification, as well as the models, systems, and perspectives it utilizes. The following parts discuss the various types of repair including base excision, nucleotide excision repair in bacteria, excision repair in mammalian cells, inducible/error-prone repair in prokaryotes, and strand break repair in mammalian cells among others. This reference material looks into the replicative bypass mechanisms in mammalian cells, viral probes, and hereditary repair defects. It explains repair deficiency and human disease, as well as mutagenesis and carcinogenesis. The last part of this book deals with the consequences and effects of DNA repair. This volume is a helpful source of reference for students, teachers, scientists, and researchers in the different fields of genetics, radiology, biochemistry, and environmental biology.

This book is based on the papers presented at the conference on "Mecha nisms of DNA Damage and Repair: Implications for Carcinogenesis and Risk Assessment," held at the National Bureau of Standards on June 2-7, 1985, This volume deals with mechanisms of DNA damage and repair at the molecular level; consequences of unrepaired or misrepaired damage, with major emphasis on carcinogenesis; drugs which bind selectively to altered and potentially damaging DNA sequences; and potential utilization of DNA damage as an endpoint for assessing risks of UV light, ionizing radiations, chemicals, drugs, and hazardous agents in foods. Because the induction of mutations by radiation and genotoxic chemicals has been observed to follow one-hit kinetics in some instances, it is generally assumed that any level of exposure to a DNA-damaging agent may increase the risk of genetic disease or cancer in an exposed population. At the same time, however, there is evidence that although the DNA of living cells is continually damaged by natural background radiation, free radicals, and other naturally occurring processes, most of the damage is normally repaired.

Cutting edge reviews by leading researchers illuminate key aspects of DNA repair in mammalian systems and its relationship to human genetic disease and cancer. Major topics include UV and X-Ray repair, repair of chemical damage, recombinational repair, mismatch repair, transcription-repair coupling, and the role of DNA repair in disease prevention. Extensive up-to-date references and rigorous peer-review of each chapter make this volume definitive and bring it to the active frontiers of research.

DNA is the central repository of genetic information in the cell, yet it is under constant attack by chemical mutagens, radiation and other processes. Cells therefore put a great deal of resources into repairing any damage to this precious store. Mechanisms of DNA repair vary greatly in their level of complexity, from specific reversal mechanisms that involve a single protein, to sequential pathways that require many enzymes. But at the heart of all these mechanisms lie proteins that recognize damage to DNA, raising important questions about how damaged DNA may be distinguished. These recognition processes are now finally yielding their secrets to structural analysis. This volume focuses on DNA repair, with an emphasis on structural data where available.