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

Authors: Hassan, Bachar H; Lindsey-Boltz, Laura A; Kemp, Michael G; Sancar, Aziz

Published In J Biol Chem, (2013 Jun 28)

Abstract: TopBP1 (topoisomerase IIβ-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.

PubMed ID: 23696651 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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