Interaction of Chk1 with treslin negatively regulates the initiation of chromosomal DNA replication Journal Article
| Authors: | Guo, C.; Kumagai, A.; Schlacher, K.; Shevchenko, A.; Dunphy, W. G. |
| Article Title: | Interaction of Chk1 with treslin negatively regulates the initiation of chromosomal DNA replication |
| Abstract: | Treslin helps to trigger the initiation of DNA replication by promoting integration of Cdc45 into the replicative helicase. Treslin is a key positive-regulatory target of cell-cycle control mechanisms; activation of Treslin by cyclin-dependent kinase is essential for the initiation of replication. Here we demonstrate that Treslin is also a critical locus for negative regulatory mechanisms that suppress initiation. We found that the checkpoint-regulatory kinase Chk1 associates specifically with a C-terminal domain of Treslin (designated TRCT). Mutations in the TRCT domain abolish binding of Chk1 to Treslin and thereby eliminate Chk1-catalyzed phosphorylation of Treslin. Significantly, abolition of the Treslin-Chk1 interaction results in elevated initiation of chromosomal DNA replication during an unperturbed cell cycle, which reveals a function for Chk1 during a normal S phase. This increase is due to enhanced loading of Cdc45 onto potential replication origins. These studies provide important insights into how vertebrate cells orchestrate proper initiation of replication. © 2015 Elsevier Inc. |
| Keywords: | controlled study; human tissue; protein phosphorylation; unclassified drug; human cell; chromosome mutation; dna replication; chromosome; cell cycle s phase; carboxy terminal sequence; protein protein interaction; protein; vertebrata; dna; checkpoint kinase 1; enzyme binding; vertebrate; genetic regulation; human; article; treslin protein |
| Journal Title: | Molecular Cell |
| Volume: | 57 |
| Issue: | 3 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2015-02-05 |
| Start Page: | 492 |
| End Page: | 506 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2014.12.003 |
| PROVIDER: | scopus |
| PMCID: | PMC4321788 |
| PUBMED: | 25557548 |
| DOI/URL: | |
| Notes: | Export Date: 2 April 2015 -- Source: Scopus |
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