Thymineless Death Lives On: New Insights into a Classic Phenomenon

Arkady Khodursky, Elena C. Guzmán, Philip C. Hanawalt

Research output: Contribution to journalReview articlepeer-review

29 Scopus citations

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. ©

Original languageEnglish (US)
Pages (from-to)247-263
Number of pages17
JournalAnnual Review of Microbiology
Volume69
Issue number1
DOIs
StatePublished - Oct 15 2015

Keywords

  • DNA degradation
  • DNA replication
  • Replication fork
  • Replication origins
  • TLD
  • Thymidylate synthase
  • Thymine deficiency
  • Thymineless death
  • Transcription

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