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Colonic Lysine Homocysteinylation Induced by High-Fat Diet Suppresses DNA Damage Repair.

Cell Rep. 2018; 
Wang D, Zhao R, Qu YY, Mei XY, Zhang X, Zhou Q, Li Y, Yang SB, Zuo ZG, Chen YM, Lin Y, Xu W, Chen C, Zhao SM, Zhao JY.
Products/Services Used Details Operation
Peptide Synthesis X(Ser139) Cell Signaling Technology Cat#9718; RRID: AB_2118009 Phospho SQ/TQ ATM/ATR Substrate Abcam Cat#ab130947 MARS Abcam Cat#ab50793; RRID: AB_881492 CHK2 Abcam Cat#ab47433; RRID: AB_869138 CHK2(phospho-Thr68) Abcam Cat#ab3501; RRID: AB_449196 RPA32/RPA2 Abcam Cat#ab2175; RRID: AB_302873 Flag Abmart Cat#M20008; RRID: AB_2713960 Myc Abmart Cat#M20002 Actin GenScript Cat#A00702-100; RRID: AB_914102 Anti-mouse secondary antibodies GenScript Cat#A00160; RRID: AB_1968937 Anti-rabbit secondary antibodies GenScript Cat#A00098; RRID: AB_1968815 Hcy-K antibody This Study N/A Chemicals, Peptides, and Recombinant Proteins Hydroxyurea Sigma Cat#H8627 sequencing grade modified trypsin Promega Cat#V5111 L-Homocysteine Sigma Cat#44925 Anti-FLAG M2 Magnetic Beads Sigma Cat#M8823 iQ SYBR Green Supermix Bio-rad Cat#170884 Critical Commercial Assays FITC Annexin V Apoptosis Detection Kit I BD PharMingen Cat#556547 Comet Assay Kit Trevigen Cat#4250-050-K QIAamp DNA Mini Kit QIAGEN Cat#51306 DNA Damage-AP sites-Assay kit Abcam Cat#ab211154 Cell Counting Kit-8 Dojindo Cat#CK04 Experimental Models: Cell Lines Human:HCT116 ATCC ATCC number: CCL-247 Human:A549 ATCC ATCC number: CCL-185 Experimental Models: Organisms/Strains ICR Shanghai SLAC Laboratory Animal Co. Get A Quote

摘要

Colorectal cancer (CRC) onset is profoundly affected by Western diet. Here, we report that high-fat (HF) diet-induced, organ-specific colonic lysine homocysteinylation (K-Hcy) increase might promote CRC onset by impeding DNA damage repair. HF chow induced elevated methionyl-tRNA synthetase (MARS) expression and K-Hcy levels and DNA damage accumulation in the mouse and rat colon, resulting in a phenotype identical to that of CRC tissues. Moreover, the increased copy number of MARS, whose protein product promotes K-Hcy, correlated with increased CRC risk in humans. Mechanistically, MARS preferentially bound to and modified ataxia-telangiectasia and Rad3-related protein (ATR), inhibited ATR and its downstream eff... More

关键词

DNA damage repair; ataxia-telangiectasia and Rad3-related protein; colorectal cancer; high-fat diet; lysine homocysteinylation