Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

TDP1 (Tyrosyl-DNA Phosphodiesterase I)

  • Selma M. Cuya
  • Robert C. A. M. van WaardenburgEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101921


Historical Background

In 1996, Howard Nash and colleagues reported the discovery of a eukaryotic enzyme activity able to hydrolyze 3′phosphotyrosyl linkages (Yang et al. 1996). Three years later, they reported the identification of the gene encoding for this enzyme activity, tyrosyl-DNA phosphodiesterase I (TDP1) (Pouliot et al. 1999). Subsequently, it was determined that TDP1 can hydrolyze many DNA adducts, including 5′phosphotyrosyl linkages. The TDP1 catalytic cycle revealed that TDP1 replaces the DNA adduct with itself following auto-hydrolysis that leaves behind nicked DNA for further processing (Fig. 1a) (for extensive TDP1 reviews, see (Comeaux and van Waardenburg 2014; Pommier et al. 2014)). TDP1 is placed in a subclass within the phospholipase D (PLD) superfamily based on the presence of two catalytic His-Lys-Asn motifs. Moreover, TDP1 is expressed in most if not all cells within the human body, and elevated...
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© Springer International Publishing AG 2018

Authors and Affiliations

  • Selma M. Cuya
    • 1
  • Robert C. A. M. van Waardenburg
    • 1
    Email author
  1. 1.Department of Pharmacology and ToxicologyUniversity of Alabama at BirminghamBirminghamUSA