One-Step Enzymatic Labeling Reveals a Critical Role of O-GlcNAcylation in Cell-Cycle Progression and DNA Damage Response

Tian，Yinping1,2; Zhu，Qiang2; Sun，Zeyu3; Geng，Didi2; Lin，Bingyi1; Su，Xiaoling3; He，Jiahui2; Guo，Miao2; Xu，Hong2; Zhao，Ye2; Qin，Weijie4; Wang，Peng George5; Wen，Liuqing6; Yi，Wen1,2

2021

10.1002/anie.202110053

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   影响因子和分区

1433-7851

1521-3773

O-linked N-acetylglucosamine (O-GlcNAcylation) is a ubiquitous post-translational modification of proteins that is essential for cell function. Perturbation of O-GlcNAcylation leads to altered cell-cycle progression and DNA damage response. However, the underlying mechanisms are poorly understood. Here, we develop a highly sensitive one-step enzymatic strategy for capture and profiling O-GlcNAcylated proteins in cells. Using this strategy, we discover that flap endonuclease 1 (FEN1), an essential enzyme in DNA synthesis, is a novel substrate for O-GlcNAcylation. FEN1 O-GlcNAcylation is dynamically regulated during the cell cycle. O-GlcNAcylation at the serine 352 of FEN1 disrupts its interaction with Proliferating Cell Nuclear Antigen (PCNA) at the replication foci, and leads to altered cell cycle, defects in DNA replication, accumulation of DNA damage, and enhanced sensitivity to DNA damage agents. Thus, our study provides a sensitive method for profiling O-GlcNAcylated proteins, and reveals an unknown mechanism of O-GlcNAcylation in regulating cell cycle progression and DNA damage response.

chemoenzymatic labeling enzyme engineering glycoproteins glycosylation

SCI ; EI

英语

NI论文

其他

National Science Foundation of China[91753125, 31270865, 31322019, 22007092] ; National Science Foundation of Zhejiang Province, China[LZ21C050001] ; Mizutani Foundation for Glycoscience[210036] ; National Key Research and Development Program of China[2016YFA0100303]

Chemistry

Chemistry, Multidisciplinary

WOS:000723253500019

WILEY-V C H VERLAG GMBH

20214511111936

Cell engineering ; Cell proliferation ; DNA ; Enzymes ; Glycosylation

Biomedical Engineering:461.1 ; Biological Materials and Tissue Engineering:461.2 ; Biology:461.9 ; Biochemistry:801.2 ; Organic Compounds:804.1

CHEMISTRY

2-s2.0-85118502012

Scopus

1.Department of Hepatobiliary and Pancreatic Surgery,The First Affiliated Hospital,Zhejiang Provincial Key Laboratory of Pancreatic Disease,School of Medicine,Zhejiang University,Hangzhou,China
2.MOE Key Laboratory of Biosystems Homeostasis & Protection,College of Life Sciences,Zhejiang University,Hangzhou,China
3.State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,National Clinical Research Center for Infectious Diseases,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease,The First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou,China
4.National Center for Protein Sciences Beijing,State Key Laboratory of Proteomics,Beijing Proteome Research Center,Beijing Institute of Lifeomics,Beijing,China
5.School of Medicine,Southern University of Science and Technology,Shenzhen,China
6.Carbohydrate-Based Drug Research Center,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,China

Tian，Yinping,Zhu，Qiang,Sun，Zeyu,et al. One-Step Enzymatic Labeling Reveals a Critical Role of O-GlcNAcylation in Cell-Cycle Progression and DNA Damage Response[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2021,60(50):26128-26135.

Tian，Yinping.,Zhu，Qiang.,Sun，Zeyu.,Geng，Didi.,Lin，Bingyi.,...&Yi，Wen.(2021).One-Step Enzymatic Labeling Reveals a Critical Role of O-GlcNAcylation in Cell-Cycle Progression and DNA Damage Response.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,60(50),26128-26135.

Tian，Yinping,et al."One-Step Enzymatic Labeling Reveals a Critical Role of O-GlcNAcylation in Cell-Cycle Progression and DNA Damage Response".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 60.50(2021):26128-26135.