title: Regulation of ATRIP protein abundance by RAD9 in the DNA damage repair pathway.
abstract: Genotoxic stress activates checkpoint signaling pathways that activate the checkpoint kinases ATM and ATR, halt cell cycle progression, and promote DNA repair. A number of proteins act in concert with ATR to phosphorylate Chk1, including RAD17, the RAD9-RAD1-HUS1 complex, ATR/ATRIP and TopBp1. However, how these proteins involved act in concert with one another to propagate and maintain the checkpoint response is not well understood. Here, we reported that upregulation of RAD9 protein increased the quantity of ATRIP, suggesting that RAD9 activation will induce more efficient accumulation of ATRIP in vivo. Furthermore, the DNA damage-induced ATRIP foci formation was faster in the mRad9-/- ES cells. Also, ATRIP interacts specifically with RAD9, but not HUS1 and RAD1. Taken together, we suggested that RAD9 could affect both the ATRIP protein levels and DNA damage-induced ATRIP foci formation. Thus, we propose a role of RAD9 in the ATR-Chk1 pathway that is necessary for successful formation of the damage-sensing complex and DNA damage checkpoint signaling.
authors.affiliation: Nanchang University School of Life Sciences and Institute of Life Science Nanchang China.
authors.forename: X-J
authors.initials: XJ
authors.lastname: Peng
authors.affiliation: Nanchang University School of Life Sciences and Institute of Life Science Nanchang China.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Liu
authors.affiliation: Nanchang University School of Life Sciences and Institute of Life Science Nanchang China.
authors.forename: C-M
authors.initials: CM
authors.lastname: Bao
authors.affiliation: Nanchang University School of Life Sciences and Institute of Life Science Nanchang China.
authors.forename: Y-Z
authors.initials: YZ
authors.lastname: Liu
authors.affiliation: Jiangxi Academy of Agricultural Sciences Jiangxi Super&mdash;rice Research and Development Center Nanchang China.
authors.forename: H-W
authors.initials: HW
authors.lastname: Xie
authors.affiliation: Jiangxi Academy of Agricultural Sciences Jiangxi Super-rice Research and Development Center Nanchang China.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Cai
authors.affiliation: Nanchang University School of Life Sciences and Institute of Life Science Nanchang China.
authors.forename: B-M
authors.initials: BM
authors.lastname: Li
authors.affiliation: Chinese Academy of Sciences Center for Infection and Immunity, Institute of Biophysics Beijing China.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Hang
authors.affiliation: Nanchang University School of Life Sciences and Institute of Life Science Nanchang China dingxia97@ncu.edu.cn.
authors.forename: X
authors.initials: X
authors.lastname: Ding
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D000071877:Checkpoint Kinase 1; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005092:Exonucleases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013045:Species Specificity
chemical_list: C521194:ATRIP protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; C549605:HUS1 protein, human; D009687:Nuclear Proteins; C110513:TOPBP1 protein, human; C069930:rad9 protein; D004247:DNA; D011494:Protein Kinases; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; C000605869:Chek1 protein, mouse; D005092:Exonucleases; C113574:Rad1 protein, human; D006918:Hydroxyurea