CLSPN

The product of this gene is an essential upstream regulator of checkpoint kinase 1 and triggers a checkpoint arrest of the cell cycle in response to replicative stress or DNA damage. The protein is also required for efficient DNA replication during a normal S phase. Multiple transcript variants encoding different isoforms have been found for this gene.

Full Name

Claspin

Function

Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation. Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins. Can also bind specifically to branched DNA structures and may associate with S-phase chromatin following formation of the pre-replication complex (pre-RC). This may indicate a role for this protein as a sensor which monitors the integrity of DNA replication forks.

Biological Process

Activation of protein kinase activity Source: UniProtKB
DNA damage checkpoint Source: UniProtKB
DNA repair Source: UniProtKB-KW
DNA replication Source: Reactome
DNA replication checkpoint Source: MGI
Mitotic DNA replication checkpoint Source: UniProtKB
Mitotic G2 DNA damage checkpoint Source: UniProtKB
Peptidyl-serine phosphorylation Source: UniProtKB
Protein deubiquitination Source: Reactome

Cellular Location

Nucleus

PTM

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.