claspin; hclaspin (CLSPN)

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Function

required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing & UV irradiation
adapter protein which binds to BRCA1 & the checkpoint kinase CHEK1 & facilitates the ATR-dependent phosphorylation of both proteins
can also bind specifically to branched DNA structures & may associate with S-phase chromatin following formation of the pre-replication complex
this may indicate a role for this protein as a sensor which monitors the integrity of DNA replication forks
phosphorylated
undergoes ATR-dependent phosphorylation by CHEK1 during activation of DNA replication or damage checkpoints
phosphorylation by CSNK1G1/CK1 promotes CHEK1 binding
ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) during G1 phase, leading to its degradation by the proteasome
ubiquitination is mediated via its interaction with FZR1/CDH1
following DNA damage, it is deubiquitinated by USP28 in G2 phase, preventing its degradation
interacts (phosphorylation-dependent) with CHEK1
regulates CLSPN function in checkpoint for DNA damage & replication
interacts with ATR & RAD9A; these interactions are slightly reduced during checkpoint activation
interacts with BRCA1; interaction increases during checkpoint activation
interacts with TIMELESS

the C-terminus of the protein contains 3 potential CHEK1- binding motifs (CKB motifs)
potential phosphorylation sites within CKB motif 1 & CKB motif 2 are required for interaction with CHEK1
belongs to the claspin family