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Two different ubiquitin ligases control the abundance of Claspin at different phases of the cell cycle
Author(s) -
Pagano Michele,
Bassermann Florian,
Peschiaroli Angelo
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a154
Subject(s) - cell cycle checkpoint , dna damage , g2 m dna damage checkpoint , cell cycle , chek1 , microbiology and biotechnology , checkpoint kinase 2 , ubiquitin , effector , proteolysis , degron , phosphorylation , kinase , dna replication , biology , cell cycle protein , chemistry , dna , ubiquitin ligase , cell , genetics , biochemistry , gene , enzyme
DNA‐damage checkpoints ensure genomic integrity by mediating cell‐cycle arrest in response to genotoxic stress or stalled replication forks. In response to damage, the checkpoint kinase ATR phosphorylates and activates its effector kinase Chk1, a process mediated by Claspin. We found that the recovery from the DNA replication checkpoint in G2 phase relies on the ubiquitin‐mediated degradation of Claspin. This process is ?Trcp‐dependent and requires the PLK1‐dependent phosphorylation of Claspin at a canonical DSGxxS degron. Importantly, in response to DNA damage in G2, Claspin proteolysis is inhibited to allow the prompt reestablishment of the checkpoint. We will present data on a ßTrcp‐independent mechanism that controls the degradation of Claspin during the G1 phase of the cell cycle. This finding may shed light on how Chk1 activity is repressed in G1 phase.