An article published this year in “JOURNAL OF CELL BIOLOGY” using our Cell Cycle Analysis
(PI / RNASE) solution, by our customers from State Key Laboratory of Drug Research, Shanghai
Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China, in
the study of how Phosphoglycerate mutase 1 regulates dNTP pool and promotes
homologous recombination repair in cancer cells. Congrats and Thanks.
Summary:
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 in cancer cells. Herein, we report that PGAM1 is required
for homologous recombination (HR) repair of DNA double-strand breaks (DSBs)
caused by DNA-damaging agents. Mechanistically, PGAM1 facilitates DSB end
resection by regulating the stability of CTBP-interacting protein (CtIP).
Knockdown of PGAM1 in cancer cells accelerates CtIP degradation through
deprivation of the intracellular deoxyribonucleotide triphosphate pool and
associated activation of the p53/p73 pathway. Enzymatic inhibition of PGAM1
decreases CtIP protein levels, impairs HR repair, and hence sensitizes
BRCA1/2-proficient breast cancer to poly(ADP-ribose) polymerase (PARP)
inhibitors. Together, this study identifies a metabolically dependent function
of PGAM1 in promoting HR repair and reveals a potential therapeutic opportunity
for PGAM1 inhibitors in combination with PARP inhibitors.
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