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• W2154713717 abstract "Adeno-associated virus Rep78 protein has antiproliferative effects on cells. It inhibits cell cycle progression, and, in particular, Rep78 induces a complete arrest within S phase, a response rarely seen after cell DNA damage. We examined how Rep78 achieves such an efficient S phase block. Rep78 inhibits Cdc25A activity by a novel means in which binding between the two proteins stabilizes Cdc25A, thus increasing its abundance, while at the same time preventing access to its substrates cyclin-dependent kinase (Cdk) 2 and Cdk1. This effect alone does not induce a complete S phase block. In addition, Rep78, as well as Rep68, produces nicks in the cellular chromatin, inducing a DNA damage response mediated by ataxia telangiectasia mutated (ATM) leading to G 1 and G 2 blocks. Mutational analysis shows that the zinc finger domain and nuclease activity of Rep78 are both required for the S phase block. The results suggest that a true S phase block cannot be achieved through a single pathway, and that adeno-associated virus Rep78 protein arrests cells within S phase by interfering with two pathways that would normally lead to an S phase slow-down." @default.
• W2154713717 created "2016-06-24" @default.
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• W2154713717 date "2005-09-12" @default.
• W2154713717 modified "2023-09-30" @default.
• W2154713717 title "How adeno-associated virus Rep78 protein arrests cells completely in S phase" @default.
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• W2154713717 doi "https://doi.org/10.1073/pnas.0504583102" @default.
• W2154713717 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1224635" @default.
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