The Xenopus Xmus101 protein is required for the recruitment of Cdc45 to origins of DNA replication

By Ruth A. Van Hatten, Antonin Tutter, A. Holway, Alyssa M. Khederian, Johannes C. Walter, W. Michael. 2002

145 citations recorded by the source corpus.

The initiation of eukaryotic DNA replication involves origin recruitment and activation of the MCM2-7 complex, the putative replicative helicase. Mini-chromosome maintenance (MCM)2-7 recruitment to origins in G1 requires origin recognition complex (ORC), Cdt1, and Cdc6, and activation at G1/S requires MCM10 and the protein kinases Cdc7 and S-Cdk, which together recruit Cdc45, a putative MCM2-7 cofactor required for origin unwinding. Here, we show that the Xenopus BRCA1 COOH terminus repeat–containing Xmus101 protein is required for loading of Cdc45 onto the origin. Xmus101 chromatin association is dependent on ORC, and independent of S-Cdk and MCM2-7. These results define a new factor that is required for Cdc45 loading. Additionally, these findings indicate that the initiation complex assembly pathway bifurcates early, after ORC association with the origin, and that two parallel pathways, one controlled by MCM2-7, and the other by Xmus101, cooperate to load Cdc45 onto the origin.

Subfields: Cancer Research, 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
6. Andrej Shevchenko
7. J. Lees

Citations in the corpus

• DONSON facilitates Cdc45 and GINS chromatin association and is essential for DNA replication initiation (2023, background): “Previous studies concerning TopBP1 howe v er, showed tha t chroma tin binding was either unaffected by all such treatments ( 47 ) or reduced to different le v els by all of them ( 18 , 46 ).”
• Efficient Initiation of DNA Replication in Eukaryotes Requires Dpb11/TopBP1-GINS Interaction (2013, background): “Division of Microbial Genetics, National Institute of Genetics,a and Department of Genetics, School of Life Science, SOKENDAI,b Shizuoka, Japan; Graduate School of Science, Osaka University, Osaka, Japanc Dpb11/Cut5/TopBP1 is evolutionarily conserved and is essential for the initiation of DNA replic”
• A vertebrate gene, ticrr, is an essential checkpoint and replication regulator. (2010, background): “Consistent with these observations, TopBP1 associates with Cdc45, and the recruitment of TopBP1, Cdc45, and GINS that is required for the pre-RCto-pre-IC transition appears to be interdependent (Van Hatten et al. 2002; Kubota et al. 2003; Takayama et al. 2003; Schmidt et al. 2008).”
• Treslin Collaborates with TopBP1 in Triggering the Initiation of DNA Replication (2010, background): “Vanadate is an inhibitor of lambda phosphatase.”
• The N-Terminal Noncatalytic Region of Xenopus RecQ4 Is Required for Chromatin Binding of DNA Polymerase α in the Initiation of DNA Replication (2006, background): “Studies with metazoan homologs of Dpb11, in particular with Xenopus laevis Cut5/Mus101, support this view, showing that the metazoan protein is required for the loading of DNA polymerases onto chromatin (8, 33).”
• Novel role of DONSON in CMG helicase assembly during vertebrate DNA replication initiation (2023, unknown): “Vertebrate Treslin, MTBP, and TopBP1 are the functional counterparts of yeast Sld3, Sld7, and Dpb11, respectively (Van Hatten et al, 2002; Kumagai et al, 2010; Sansam et al, 2010; Boos et al, 2013).”