DNA 損傷チェックポイントとがん - jbsoc.or.jp

1 Pp.. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! !!! !!! . !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! DNA . Chk .. DNA ATM-Chk -p . ATR-Chk -Cdc . A . ATM-Chk - p . DNA . ATR-Chk -Cdc . A Chk .. Chk ATR . Chk . Chk .. DNA . DNA DNA .. DNA DNA . G S S CDK cyclin-dependent kinase . G M DNA . DNA . ATM ataxia-telangiectasia mutated . DNA . -Chk checkpoint kinase . -p .. DNA . ATM Chk p .. p . p .. p . CDK . DNA damage checkpoint and cancer pros and cons of Chk . inhibitors . Hidemasa Goto and Masaki Inagaki Division of Bio- G S . chemistry, Aichi Cancer Center Research Institute, . Kanokoden, Chikusa-ku, Nagoya, Aichi , Japan, .. Department of Cellular Oncology, Nagoya University Graduate School of Medicine, . Tsurumai-cho, Showa-ku, ATR ATM- and Nagoya, Aichi , Japan Rad -related; ATM Rad.

2 -Chk .. DNA .. checkpoint kinase . -Cdc . A. DNA Chk . S DNA G M.. DNA DNA ATR. ATR-Chk -Cdc . A .. ATR ATR ATRIP ATR-interacting pro- DNA Chk tein RPA replication protein A . DNA DNA .. mitotic catastrophe DNA . DNA . Chk I II RAD . RAD -HUS -RAD .. - - . RPA DNA. Chk ATR RAD . ATR RAD . DNA TOPBP DNA topoisomerase II binding protein ATR TOPBP .. Chk ATR ATR TOPBP . Chk TOPBP . ATR DNA . DNA Chk ATR. Chk Chk . Claspin Claspin . TIM Timeless . TIPIN TIM-interacting protein . TIPIN RPA.. DNA ATR-Chk . P . DNA Chk .. ATR Chk . Cdc . A .. DNA Chk Cdc .. - - . Chk ATR . Chk Cdc . A Chk .. - - . DNA . DNA Chk -Cdc . A .. Chk DNA . DNA CHEK .. ATR Chk .. Chk . CHEK . Chk S G S .. S DNA DNA . ATR Chk DNA G M.. Chk Chk . S . Chk DNA Chk G S G.

3 DNA . Chk . DNA .. - - Chk Cdc .. - - Cdc . A CDK CDK .. - - Chk . Chk Cdc . A . - - CDK G M .. Chk Cdc . A .. Cdc . A .. C -TrCP phos- G M CDK . phodegron F-box Chk .. -TrCP .. Chk . Crm- chromosome region maintenance protein .. Chk NEK .. NIMA . Chk CDK . A SCF -TrCP Skp-Cullin-F-box . Cdc . F-box . -TrCP S . A S . A . CDK Chk CDK . Chk - . Cdc . A Chk - . G M Cdk Chk .. - - . Chk - .. DNA CDK . Chk .. Chk G Chk Chk . Chk .. Chk . Chk . Chk DNA . Chk G S G . CHEK . Chk Chk . S DNA . G .. CDK Chk . CDK G M . Chk Cdc . CDK CDK Chk . Chk Crm- . Chk Chk . CDK CDK . CDK Chk . Chk Chk . G . Chk . Chk . Chk .. MAPK mitogen-activated pro- . tein kinase p . RSK . kDa DNA . ribosomal S kinase .. Chk .. DNA . Chk .. ATR Chk ATM- .. Chk -p.

4 ATR-Chk -Cdc . A . DNA DNA .. p . RSK Chk ATM-Chk -p .. DNA .. Chk ATM CHEK TP .. Chk - . Chk .. Chk . ATM-Chk -p .. G S Chk .. ATR-Chk -Cdc . A . Chk .. ATR-Chk -Cdc . A DNA . DNA ATM- Chk . Chk -p . Chk ATR . Chk . Chk . Chk Chk .. DNA . Chk Chk . ATR-Chk -Cdc . A Chk . ATM-Chk -p . ATR-Chk -Cdc . A Chk .. Chk DNA .. Chk .. Chini, & Chen, J. J. Biol. Chem., , .. Kumagai, A., Kim, , & Dunphy, J. Biol. Chem., , . Jackson, & Bartek, J. Nature, , .. Kemp, , Akan, Z., Yilmaz, S., Grillo, M., Smith-Roe, S. Ciccia, A. & Elledge, Mol. Cell, , . L., Kang, , Cordeiro-Stone, M., Kaufmann, , Abraham, Bartek, J. & Lukas, J. Curr. Opin. Cell Biol., , , Sancar, A., & Unsal-Kacmaz, K. J. Biol. Chem., . , . Medema, & Macurek, L. Oncogene.

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