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Human Cdc25 A inactivation in response to S phase inhibition and its role in preventing premature mitosis
Author(s) -
Molinari Marta,
Mercurio Ciro,
Dominguez Jorge,
Goubin Francoise,
Draetta Giulio F
Publication year - 2000
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kvd018
Subject(s) - mitosis , biology , microbiology and biotechnology , phase (matter) , chemistry , organic chemistry
The Cdc25 A phosphatase is required for the G 1 –S transition of the cell cycle and is overexpressed in human cancers. We found that it is ubiquitylated and rapidly degraded by the proteasome and that its levels increase from G 1 until mitosis. By treating cells with the DNA synthesis inhibitor hydroxyurea, Cdc25 A rapidly decreased in abundance, and this was accompanied by an increase in Cdk2 phosphotyrosine content and a decrease in Cdk2 kinase activity. Cdc25 A overexpression altered the ability of cells to arrest in the presence of hydroxyurea, and caused them to undergo premature chromosome condensation. Cdc25 A overexpression could render tumor cells less sensitive to DNA replication checkpoints, thereby contributing to their genomic instability.