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MTBP, the Partner of Treslin, Contains a Novel DNA-Binding Domain, That Is Essential for Proper Initiation of DNA Replication

Kumagai, Akiko and Dunphy, William G. (2017) MTBP, the Partner of Treslin, Contains a Novel DNA-Binding Domain, That Is Essential for Proper Initiation of DNA Replication. Molecular Biology of the Cell, 28 (22). pp. 2998-3012. ISSN 1059-1524. PMCID PMC5662258.

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Treslin, which is essential for incorporation of Cdc45 into the replicative helicase, possesses a partner called MTBP. We have analyzed Xenopus and human MTBP to assess its role in DNA replication. Depletion of MTBP from Xenopus egg extracts, which also removes Treslin, abolishes DNA replication. These extracts be can rescued with recombinant Treslin-MTBP, but not Treslin or MTBP alone. Thus, Treslin-MTBP is collectively necessary for replication. We have identified a C-terminal region of MTBP (the CTM domain) that binds efficiently to both double-stranded DNA and G-quadruplex (G4) DNA. This domain also exhibits homology with budding yeast Sld7. Mutants of MTBP without a functional CTM domain are defective for DNA replication in Xenopus egg extracts. These mutants display an impaired localization to chromatin and the inability to support loading of Cdc45. Human cells harboring such a mutant also display severe S-phase defects. Thus, the CTM domain of MTBP plays a critical role in localizing Treslin-MTBP to the replication apparatus for initiation.

Item Type:Article
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URLURL TypeDescription Material CentralArticle
Kumagai, Akiko0000-0003-2422-8053
Dunphy, William G.0000-0001-7598-8939
Additional Information:© 2017 by The American Society for Cell Biology. Free via Creative Commons 2 months after publication. Submitted July 10, 2017; Revised August 30, 2017; Accepted August 31, 2017. Published online before print September 6, 2017. We are grateful to Kanomi Sasaki-Capela and Bashar Alhoch for technical assistance. We also thank Rochelle Diamond for assistance with the FACS analyses. Imaging studies were performed in the Caltech Biological Imaging Center, which is supported by the Beckman Institute and the Arnold and Mabel Beckman Foundation. We are also grateful to Lea Goentoro for access to the Zeiss AxioObserver.Z1 microscope. This work was supported by National Institutes of Health grants GM-043974 and GM-070891 to W.G.D. Author contributions: A.K. and W.G.D. conceived the study. A.K. carried out the experiments. A.K. and W.G.D. wrote the paper.
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Caltech Beckman InstituteUNSPECIFIED
Arnold and Mabel Beckman FoundationUNSPECIFIED
Issue or Number:22
PubMed Central ID:PMC5662258
Record Number:CaltechAUTHORS:20170912-102544473
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Official Citation:Akiko Kumagai and William G. Dunphy MTBP, the partner of Treslin, contains a novel DNA-binding domain that is essential for proper initiation of DNA replication Mol. Biol. Cell 2017 28:22 2998-3012; First Published on September 6, 2017; doi:10.1091/mbc.E17-07-0448
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:81356
Deposited By: Tony Diaz
Deposited On:12 Sep 2017 17:45
Last Modified:09 Mar 2020 13:18

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