Treslin Collaborates with TopBP1 in Triggering the Initiation of DNA Replication

By A. Kumagai, Andrej Shevchenko, W. G. Dunphy. 2010

255 citations recorded by the source corpus.

SUMMARY TopBP1 has important roles in both DNA replication and checkpoint regulation in vertebrates. We have identified a protein called Treslin that associates with TopBP1 in Xenopus egg extracts. Depletion of Treslin from egg extracts strongly inhibits chromosomal DNA replication. Binding of Treslin to chromatin in egg extracts occurs independently of TopBP1. However, loading of the initiator protein Cdc45 onto chromatin cannot take place in the absence of Treslin. Prior to the initiation of DNA replication, Treslin associates with TopBP1 in a Cdk2-dependent manner. Ablation of Treslin from human cells also strongly inhibits DNA replication. Taken together, these results indicate that Treslin and TopBP1 collaborate in the Cdk2-mediated loading of Cdc45 onto replication origins. Thus, Treslin regulates a pivotal step in the initiation of DNA replication in vertebrates.

Subfields: Cell Biology, Molecular Biology

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In Cell Biology

1. W. G. Dunphy
2. A. Kumagai
3. Y. Kubota
4. Hiroyuki Araki
5. H. Takisawa

In Molecular Biology

1. A. Kumagai
2. W. G. Dunphy
3. Y. Kubota
4. Hiroyuki Araki
5. H. Takisawa

Citations in the corpus

• In silico protein interaction screening uncovers DONSON’s role in replication initiation (2023, neutral): “Furthermore, analogous to Sld3 ′ s interaction with Dpb11, CDK-phosphorylated TRESLIN binds to Dpb11 ’ s ortholog, TOPBP1 ( 8 , 13 – 15 ).”
• DNSN-1 recruits GINS for CMG helicase assembly during DNA replication initiation in C. elegans (2023, unknown): “Finally, the metazoan orthologue of yeast Dpb11, known variously as TOPBP1 or MUS101, contains more BRCT domains than Dpb11 (31), and a study of Xenopus TOPBP1 indicated that BRCTs 4-8 are dispensable for replication initiation (32), despite containing the presumed binding site for RECQL4.”
• Phosphorylation-dependent assembly of DNA damage response systems and the central roles of TOPBP1 (2021, background): “While this model holds for TOPBP1 roles in DNA damage signalling, the AAD seems to be dispensable for its role in CMG assembly [93].”
• DONSON facilitates Cdc45 and GINS chromatin association and is essential for DNA replication initiation (2023, background): “Their interaction is strengthened by DDK activity but does not r equir e CDK activity; on the contrary, they are hyper-loaded upon inhibition of CDKs ( 18 , 46 ).”
• MTBP, the partner of Treslin, contains a novel DNA-binding domain that is essential for proper initiation of DNA replication (2017, methodology): “Xenopus egg extracts Whole cytoplasmic extracts from Xenopus laevis eggs were prepared as before (Kumagai et al., 2010).”
• Efficient Initiation of DNA Replication in Eukaryotes Requires Dpb11/TopBP1-GINS Interaction (2013, background): “However, BRCT4 and -5 in vertebrate TopBP1, which correspond to BRCT3 and -4 of yeast Dpb11/Cut5, are dispensable for DNA replication (20).”