@article{oai:repo.qst.go.jp:00043294, author = {Watanabe, Fumiaki and Shinohara, Ken-ichi and Teraoka, Hirobumi and Komatsu, Kenshi and Tatsumi, Kouichi and Suzuki, Fumio and Imai, Takashi and Sagara, Masashi and Tsuji, Hideo and Ogiu, Toshiaki and 巽 紘一 and 今井 高志 and 相良 雅史 and 辻 秀雄 and 荻生 俊昭}, journal = {The International Journal of Biochemistry & Cell Biology}, month = {Apr}, note = {The catalytic polypeptide of DNA-dependent protein kinase (p470) is encoded by the gene responsible for murine severe combined immunodeficiency (SCID) devoid of DNA double-strand break repair and V(D)J recombination. Here, we have characterized the role of p470 in cell proliferation using SCID mice and the cell lines. In accord with DNA histogram patterns, SCID cell lines (SD/SD-eA and SC3VA2) expressing extremely low level of DNA-PK activity grew faster than a normal mouse cell line (CB/CB-eB) and SC3VA2 complemented with human p470 gene (RD13B2). In regenerating liver after partial hepatectomy, de novo DNA synthesis determined by [(3)H]thymidine incorporation started at 30h in C.B-17/Icr-SCID (SCID) mice and at around 36h in C.B-17/Icr (C.B-17) mice. Compared with normal cells, SCID cells contained slightly higher levels of transcripts of cyclin A, cyclin E, B-Myb and dihydrofolate reductase, which are regulated by E2F-1. E2F-1 playing a key role in G1- to S-phase progression was phosphorylated in vitro by DNA-PK. Importantly, the E2F-1 promoter transcriptional activity in SCID cell lines (SD/SD-eA and SC3VA2) was 4-5-fold higher than that in CB/CB-eB and RD13B2. These results suggest that p470 is involved in down-regulation of cell cycle progression through E2F-1-responsible genes.}, pages = {432--440}, title = {Involvement of DNA-dependent protein kinase in down-regulation of cell cycle progression.}, volume = {35}, year = {2003} }