Direct role for the replication protein treslin (Ticrr) in the ATR kinase-mediated checkpoint response.

TopBP1 (topoisomerase II?-binding protein 1) is a dual replication/checkpoint protein. Treslin/Ticrr, an essential replication protein, was discovered as a binding partner for TopBP1 and also in a genetic screen for checkpoint regulators in zebrafish. Treslin is phosphorylated by CDK2/cyclin E in a cell cycle-dependent manner, and its phosphorylation state dictates ...
its interaction with TopBP1. The role of Treslin in the initiation of DNA replication has been partially elucidated; however, its role in the checkpoint response remained elusive. In this study, we show that Treslin stimulates ATR phosphorylation of Chk1 both in vitro and in vivo in a TopBP1-dependent manner. Moreover, we show that the phosphorylation state of Treslin at Ser-1000 is important for its checkpoint activity. Overall, our results indicate that, like TopBP1, Treslin is a dual replication/checkpoint protein that directly participates in ATR-mediated checkpoint signaling.
Mesh Terms:
Animals, Ataxia Telangiectasia Mutated Proteins, Carrier Proteins, Cell Cycle, Cell Cycle Proteins, Checkpoint Kinase 1, DNA Damage, DNA Replication, DNA-Binding Proteins, Gene Expression Regulation, HEK293 Cells, Humans, Mice, Mutation, NIH 3T3 Cells, Nuclear Proteins, Phosphorylation, Protein Binding, Protein Kinases, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, Signal Transduction
J Biol Chem
Date: Jun. 28, 2013
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