Activation of claspin

Stable Identifier
R-HSA-176298
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Claspin is a replication fork-associated protein important for Chk1 activation. Claspin loads onto the fork during replication origin firing and travels with the fork during DNA synthesis. Upon fork uncoupling and ATR-ATRIP binding to persistent ssDNA, the activated ATR kinase phosphorylates claspin at two primary sites. Modification increases the affinity of claspin for Chk1. Studies of human or Xenopus claspin indicate that phosphorylation of both sites is essential for significant claspin-Chk1 association. Following claspin modification by ATR, Chk1 can be transiently recruited to the stalled replication fork for subsequent phosphorylation and activation by ATR. Activation of Chk1 allows modification of additional downstream targets, thus amplifying the checkpoint signal. While much of the mechanistic information concerning claspin action has been obtained using Xenopus laevis egg extracts and Xenopus claspin, factors with similar activity have been found in various eukaryotic species including S. cerevisiae (MRC1), S. pombe (mrc1), and humans.

Activated ATR phosphorylates human claspin on two sites, threonine 916 and serine 945.

Literature References
PubMed ID Title Journal Year
15707391 DNA-dependent phosphorylation of Chk1 and Claspin in a human cell-free system

Clarke, CA, Clarke, PR

Biochem J 2005
Participants
Participant Of
Event Information
Go Biological Process
Catalyst Activity
Catalyst Activity
Title
protein serine/threonine kinase activity of ATR:ATRIP [nucleoplasm]
Physical Entity
Activity
Orthologous Events
Authored
Created