title: Thymineless Death Lives On: New Insights into a Classic Phenomenon.
abstract: The primary mechanisms by which bacteria lose viability when deprived of thymine have been elusive for over half a century. Early research focused on stalled replication forks and the deleterious effects of uracil incorporation into DNA from thymidine-deficient nucleotide pools. The initiation of the replication cycle and origin-proximal DNA degradation during thymine starvation have now been quantified via whole-genome microarrays and other approaches. These advances have fostered innovative models and informative experiments in bacteria since this topic was last reviewed. Given that thymineless death is similar in mammalian cells and that certain antibacterial and chemotherapeutic drugs elicit thymine deficiency, a mechanistic understanding of this phenomenon might have valuable biomedical applications.
authors.affiliation: Biotechnology Institute and Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, St. Paul, Minnesota 55108; email: khodu001@umn.edu.
authors.forename: Arkady
authors.initials: A
authors.lastname: Khodursky
authors.affiliation: Departamento de Bioquímica Biología Molecular y Genética, Universidad de Extremadura, 06071 Badajoz, Spain; email: eguzmac@gmail.com.
authors.forename: Elena C
authors.initials: EC
authors.lastname: Guzmán
authors.affiliation: Department of Biology, Stanford University, Stanford, California 94305; email: hanawalt@stanford.edu.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hanawalt
mesh_terms: D001419:Bacteria / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication; D004269:DNA, Bacterial / Q000378:metabolism; D004926:Escherichia coli / Q000166:cytology / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D050296:Microbial Viability; D013941:Thymine / Q000378:metabolism*
chemical_list: D004269:DNA, Bacterial; D013941:Thymine
keywords: DNA degradation; DNA replication; TLD; replication fork; replication origins; thymidylate synthase; thymine deficiency; thymineless death; transcription