ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair

Ataxia telangiectasia (A‐T) is a human disease caused by ATM deficiency characterized among other symptoms by radiosensitivity, cancer, sterility, immunodeficiency and neurological defects. ATM controls several aspects of cell cycle and promotes repair of double strand breaks (DSBs). This probably accounts for most of A‐T clinical manifestations. However, an impaired response to reactive oxygen species (ROS) might also contribute to A‐T pathogenesis. Here, we show that ATM promotes an anti‐oxidant response by regulating the pentose phosphate pathway (PPP). ATM activation induces glucose‐6‐phosphate dehydrogenase (G6PD) activity, the limiting enzyme of the PPP responsible for the production of NADPH, an essential anti‐oxidant cofactor. ATM promotes Hsp27 phosphorylation and binding to G6PD, stimulating its activity. We also show that ATM‐dependent PPP stimulation increases nucleotide production and that G6PD‐deficient cells are impaired for DSB repair. These data suggest that ATM protects cells from ROS accumulation by stimulating NADPH production and promoting the synthesis of nucleotides required for the repair of DSBs.

• Publication year

  2010

• Venue

  EMBO Journal

• Publication date

  2010-12-14

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1038/emboj.2010.330PMID 21157431PMCID 3034007
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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