2. Academic Validation
  3. An essential developmental function for murine phosphoglycolate phosphatase in safeguarding cell proliferation

An essential developmental function for murine phosphoglycolate phosphatase in safeguarding cell proliferation

  • Sci Rep. 2016 Oct 12:6:35160. doi: 10.1038/srep35160.
Gabriela Segerer 1 2,  Kerstin Hadamek 1 2,  Matthias Zundler 1 2,  Agnes Fekete 3,  Annegrit Seifried 1 2,  Martin J Mueller 3,  Frank Koentgen 4,  Manfred Gessler 5 6,  Elisabeth Jeanclos 1 2,  Antje Gohla 1 2
Affiliations

Affiliations

  • 1 Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Strasse 9, D-97078 Würzburg, Germany.
  • 2 Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Josef-Schneider-Strasse 2, D-97080 Würzburg, Germany.
  • 3 Institute of Pharmaceutical Biology, University of Würzburg, Julius-von-Sachs-Platz 2, D-97082 Würzburg, Germany.
  • 4 Ozgene Pty Ltd, PO Box 1128, Bentley DC, WA 6983, Australia.
  • 5 Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Am Hubland, University of Würzburg, D-97074 Würzburg, Germany.
  • 6 Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Strasse 6, D-97080 Würzburg, Germany.
PMID: 27731369 DOI: 10.1038/srep35160
Abstract

Mammalian phosphoglycolate Phosphatase (PGP) is thought to target phosphoglycolate, a 2-deoxyribose fragment derived from the repair of oxidative DNA lesions. However, the physiological role of this activity and the biological function of the DNA damage product phosphoglycolate is unknown. We now show that knockin replacement of murine Pgp with its phosphatase-inactive PgpD34N mutant is embryonically lethal due to intrauterine growth arrest and developmental delay in midgestation. PGP inactivation attenuated triosephosphate isomerase activity, increased triglyceride levels at the expense of the cellular phosphatidylcholine content, and inhibited cell proliferation. These effects were prevented under hypoxic conditions or by blocking phosphoglycolate release from damaged DNA. Thus, PGP is essential to sustain cell proliferation in the presence of oxygen. Collectively, our findings reveal a previously unknown mechanism coupling a DNA damage repair product to the control of intermediary metabolism and cell proliferation.

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