Phosphoglycerate mutase 1 regulates dNTP pool and promotes homologous recombination repair in cancer cells
Phosphoglycerate mutase
DOI:
10.1083/jcb.201607008
Publication Date:
2017-01-25T15:10:14Z
AUTHORS (13)
ABSTRACT
Glycolytic enzymes are known to play pivotal roles in cancer cell survival, yet their molecular mechanisms remain poorly understood. Phosphoglycerate mutase 1 (PGAM1) is an important glycolytic enzyme that coordinates glycolysis, pentose phosphate pathway, and serine biosynthesis cells. Herein, we report PGAM1 required for homologous recombination (HR) repair of DNA double-strand breaks (DSBs) caused by DNA-damaging agents. Mechanistically, facilitates DSB end resection regulating the stability CTBP-interacting protein (CtIP). Knockdown cells accelerates CtIP degradation through deprivation intracellular deoxyribonucleotide triphosphate pool associated activation p53/p73 pathway. Enzymatic inhibition decreases levels, impairs HR repair, hence sensitizes BRCA1/2-proficient breast poly(ADP-ribose) polymerase (PARP) inhibitors. Together, this study identifies a metabolically dependent function promoting reveals potential therapeutic opportunity inhibitors combination with PARP
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