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Regulation of Claspin degradation by the ubiquitin‐proteosome pathway during the cell cycle and in response to ATR‐dependent checkpoint activation
Author(s) -
Bennett Lara N.,
Clarke Paul R.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.06.071
Subject(s) - aphidicolin , proteasome , phosphorylation , cell cycle , dna damage , cell cycle checkpoint , microbiology and biotechnology , mitosis , chemistry , ubiquitin , dna , cell , biology , biochemistry , gene
Claspin is involved in ATR‐dependent activation of Chk1 during DNA replication and in response to DNA damage. We show that degradation of Claspin by the ubiquitin‐proteosome pathway is regulated during the cell cycle. Claspin is stabilized in S‐phase but is abruptly degraded in mitosis and is absent from early G 1 cells in which the phosphorylation of Chk1 by ATR is abrogated. In response to hydroxyurea, UV or aphidicolin, Claspin is phosphorylated in the Chk1‐binding domain and its protein levels are increased in an ATR‐dependent manner. Thus, the Chk1 pathway is regulated through both phosphorylation of Claspin and its controlled degradation.