Phosphoglycerate mutase 1 regulates dNTP pool and promotes homologous recombination repair in cancer cells

doi:10.1083/jcb.201607008

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	Phosphoglycerate mutase 1 regulates dNTP pool and promotes homologous recombination repair in cancer cells
	Qu, Jia 1,2; Sun, Wenyi 2; Zhong, Jie 3; Lv, Hao 2; Zhu, Mingrui 2; Xu, Jun 2; Jin, Nan 2; Xie, Zuoquan2 ; Tan, Minjia2 ; Lin, Shu-Hai 3
刊名	JOURNAL OF CELL BIOLOGY
	2017-02
卷号	216 期号:2 页码:409-424
ISSN号	0021-9525
DOI	10.1083/jcb.201607008
文献子类	Article
英文摘要	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.
资助项目	China International Science and Technology Cooperation Program[2015DFM30040] ; National Science and Technology Major Project[2015ZX09101009] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020000] ; Natural Science Foundation of China for Innovation Research Group[81321092] ; Natural Science Foundation of China[81573464] ; Natural Science Foundation of China[21377106]
WOS关键词	DNA-DAMAGE ; BREAST-CANCER ; 6-PHOSPHOGLUCONATE DEHYDROGENASE ; RIBONUCLEOTIDE REDUCTASE ; HISTONE ACETYLATION ; CELLULAR-METABOLISM ; CTIP ; P73 ; PHOSPHORYLATION ; SUPPRESSION
WOS研究方向	Cell Biology
语种	英语
出版者	ROCKEFELLER UNIV PRESS
WOS记录号	WOS:000394244800016
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275646]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Ding, Jian; Huang, Min
作者单位	1.Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210023, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Shanghai Jiao Tong Univ, Sch Med, Dept Biochem & Mol Cell Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Shanghai 200025, Peoples R China
推荐引用方式 GB/T 7714	Qu, Jia,Sun, Wenyi,Zhong, Jie,et al. Phosphoglycerate mutase 1 regulates dNTP pool and promotes homologous recombination repair in cancer cells[J]. JOURNAL OF CELL BIOLOGY,2017,216(2):409-424.
APA	Qu, Jia.,Sun, Wenyi.,Zhong, Jie.,Lv, Hao.,Zhu, Mingrui.,...&Huang, Min.(2017).Phosphoglycerate mutase 1 regulates dNTP pool and promotes homologous recombination repair in cancer cells.JOURNAL OF CELL BIOLOGY,216(2),409-424.
MLA	Qu, Jia,et al."Phosphoglycerate mutase 1 regulates dNTP pool and promotes homologous recombination repair in cancer cells".JOURNAL OF CELL BIOLOGY 216.2(2017):409-424.