"DNA damage response; Chk1 signaling; ubiquitin-specific protease; genotoxic stress"@en . "5"^^ . "184" . . . "15110" . "US - Spojen\u00E9 st\u00E1ty americk\u00E9" . "17"^^ . . . "USP7 counteracts SCF TrCP - but not APC Cdh1 -mediated proteolysis of Claspin" . "Mailand, Niels" . . . "Z(MSM6198959216)" . . "USP7 counteracts SCF TrCP - but not APC Cdh1 -mediated proteolysis of Claspin"@en . "Journal of Cell Biology" . . . "Faustrup, Helene" . "RIV/61989592:15110/09:00010975!RIV10-MSM-15110___" . "USP7 counteracts SCF TrCP - but not APC Cdh1 -mediated proteolysis of Claspin"@en . "1" . "B\u00E1rtek, Ji\u0159\u00ED" . "Claspin is an adaptor protein that facilitates the ataxia telangiectasia and Rad3-related (ATR)- mediated phosphorylation and activation of Chk1, a key effector kinase in the DNA damage response. Effi cient termination of Chk1 signaling in mitosis and during checkpoint recovery requires SCF TrCP - dependent destruction of Claspin. Here, we identify the deubiquitylating enzyme ubiquitin-specifi c protease 7 (USP7) as a novel reg ulator of Claspin stability. Claspin and USP7 interact in vivo, and USP7 is required to maintain steady-state levels of Claspin. Furthermore, USP7-mediated deubiquitylation markedly prolongs the half-life of Claspin, which in turn increases the magnitude and duration of Chk1 phosphorylation in response to genotoxic stress. Finally, we fi nd that in addition to the M phase ? specifi c, SCF TrCP -mediated degradation, Claspin is destabilized by the anaphase-promoting complex (APC) and thus remains unstable in G1. Importantly, we demonstrate that USP7 specifi cally opposes the" . . "RIV/61989592:15110/09:00010975" . . "1"^^ . . "[A51F72A18FC2]" . "Bekker-Jensen, Simon" . "0021-9525" . "Claspin is an adaptor protein that facilitates the ataxia telangiectasia and Rad3-related (ATR)- mediated phosphorylation and activation of Chk1, a key effector kinase in the DNA damage response. Effi cient termination of Chk1 signaling in mitosis and during checkpoint recovery requires SCF TrCP - dependent destruction of Claspin. Here, we identify the deubiquitylating enzyme ubiquitin-specifi c protease 7 (USP7) as a novel reg ulator of Claspin stability. Claspin and USP7 interact in vivo, and USP7 is required to maintain steady-state levels of Claspin. Furthermore, USP7-mediated deubiquitylation markedly prolongs the half-life of Claspin, which in turn increases the magnitude and duration of Chk1 phosphorylation in response to genotoxic stress. Finally, we fi nd that in addition to the M phase ? specifi c, SCF TrCP -mediated degradation, Claspin is destabilized by the anaphase-promoting complex (APC) and thus remains unstable in G1. Importantly, we demonstrate that USP7 specifi cally opposes the"@en . . "USP7 counteracts SCF TrCP - but not APC Cdh1 -mediated proteolysis of Claspin" . . . "Luk\u00E1\u0161, Ji\u0159\u00ED" . "348066" . .