This book describes genomic uracil in evolution, as a DNA constituent in adaptive and innate immune responses and as a mutagenic lesion causing cancer. Genomic uracil is as old as life and may have been a component in self-replicating molecules in the prebiotic era. The first living cells probably contained uracil in DNA, later to be replaced by thymine. The pioneering work of Nobel Laureate, Tomas Lindahl on spontaneous deamination of DNA cytosine to uracil was followed by his discovery of uracil-DNA glycosylase, which initiates repair of genomic uracil in base excision repair (BER). Uracil-DNA glycosylases are found in all forms of life and in DNA viruses, having roles in DNA repair, replication and epigenetics. The surprising discovery of enzymatic DNA cytosine deamination by the AID/APOBEC deaminases subsequently has implicated genomic uracil in the development of human cancer. The aim of the book is to contribute a reference text for graduate students, molecular biologists, immunologists and cancer biologists.
Genomic uracil has become a hot research topic of wide interest after the Nobel Prize in Chemistry 2015 was awarded for DNA repair (Paul Modrich, Aziz Sancar and Tomas Lindahl). Furthermore, genomic uracil has received wide interest among both immunologists and cancer biologists due to its unexpected and fundamental role in adaptive immunity. Genomic uracil, thus, is highly relevant to researchers in different areas of research, but to our knowledge there is no published text that treats genomic uracil in an interdisciplinary way. The authors of this book have in the last three decades worked on genomic uracil and its processing and are among the most highly cited authors in the field.
Chapter 1: Introduction — DNA Repair is Integrated with Many Cellular Processes
- Introduction — DNA Repair is Integrated with Many Cellular Processes (Hans E Krokan, Bodil Kavli and Geir Slupphaug)
- The Earth, Life and Genomic Uracil (Hans E Krokan, Bodil Kavli, Geir Slupphaug and Finn Drabløs)
- Routes to Uracil in DNA (Geir Slupphaug, Bodil Kavli and Hans E Krokan)
- Enzymology of Genomic Uracil Repair (Hans E Krokan, Bodil Kavli, Antonio Sarno and Geir Slupphaug)
- Viral Uracil — Uracil DNA Glycosylases and dUTPases (Hans E Krokan, Bodil Kavli and Geir Slupphaug)
- Genomic Uracil and Immunity (Bodil Kavli and Geir Slupphaug)
- Genomic Uracil and Cancer (Antonio Sarno, Pål Særom, Bodil Kavli and Henrik Sahlin Pettersen)
- Quantification of Genomic Uracil (Antonio Sarno and Cathrine Broberg Vågbø)
- Genomic Uracil — Valuable Tool in Molecular Biology but Inherent Problem in Sequencing of Ancient DNA (Geir Slupphaug and Hans E Krokan)
Readership: Graduate students and researchers in biochemistry, biological chemistry, cell/molecular biology, cancer research, evolution biology, genetics/genomics, analytical chemistry, immunology, oncology.
- Interdisciplinary treatment and overview of a hot topic
- No close competing text to our knowledge
- Prominent authors