title: v-Src inhibits the interaction between Rad17 and Rad9 and induces replication fork collapse.
abstract: ATR-dependent DNA damage checkpoint is crucial to maintain genomic stability. Recently, we showed that Src family kinases suppress ATR-dependent checkpoint signaling in termination of DNA damage checkpoint. However, the precise molecular mechanism is unclear. Therefore, we examined the role of oncogenic v-Src on ATR-Chk1 signaling. We show that v-Src suppresses thymidine-induced Chk1 phosphorylation and induces replication fork collapse. v-Src inhibits interaction between Rad17 and Rad9 in chromatin fraction. By contrast, v-Src does not inhibit RPA32 phosphorylation, ATR autophosphorylation, or TopBP1-Rad9 interaction. These data suggest that v-Src attenuates ATR-Chk1 signaling through the inhibition of Rad17-Rad9 interaction.
authors: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan. Electronic address: fukumoto@faculty.chiba-u.jp.
authors: Yasunori
authors: Y
authors: Fukumoto
authors: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
authors: Takahito
authors: T
authors: Miura
authors: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
authors: Mariko
authors: M
authors: Morii
authors: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
authors: Sho
authors: S
authors: Kubota
authors: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
authors: Takuya
authors: T
authors: Honda
authors: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
authors: Shoichi
authors: S
authors: Kubota
authors: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
authors: Takao
authors: T
authors: Morinaga
authors: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
authors: Noritaka
authors: N
authors: Yamaguchi
authors: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
authors: Yuji
authors: Y
authors: Nakayama
authors: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan. Electronic address: nyama@faculty.chiba-u.jp.
authors: Naoto
authors: N
authors: Yamaguchi
mesh_terms: D059447:Cell Cycle Checkpoints / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D000071877:Checkpoint Kinase 1; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; C113575:Rad17 protein, human; C069930:rad9 protein; D011494:Protein Kinases; D015688:Oncogene Protein pp60(v-src); C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1
keywords: ATR; DNA damage checkpoint; Rad17; Rad9; v-Src