Sokka M, Koalick D, Hemmerich P, Syväoja JE, Pospiech H. The ATR-Activation Domain of TopBP1 Is Required for the Suppression of Origin Firing during the S Phase. International Journal of Molecular Sciences. 2018; 19(8):2376.
The ATR-activation domain of TopBP1 is required for the suppression of origin firing during the S phase
|Author:||Sokka, Miiko1,2; Koalick, Dennis3; Hemmerich, Peter3;|
1Department of Biology, University of Eastern Finland
2Institute of Biomedicine, University of Eastern Finland
3Leibniz Institute on Aging—Fritz Lipmann Institute
4Faculty of Biochemistry and Molecular Medicine, University of Oulu
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2018101138086
Multidisciplinary Digital Publishing Institute,
The mammalian DNA replication program is controlled at two phases, the licensing of potential origins of DNA replication in early gap 1 (G1), and the selective firing of a subset of licenced origins in the synthesis (S) phase. Upon entry into the S phase, serine/threonine-protein kinase ATR (ATR) is required for successful completion of the DNA replication program by limiting unnecessary dormant origin activation. Equally important is its activator, DNA topoisomerase 2-binding protein 1 (TopBP1), which is also required for the initiation of DNA replication after a rise in S-phase kinase levels. However, it is unknown how the ATR activation domain of TopBP1 affects DNA replication dynamics. Using human cells conditionally expressing a TopBP1 mutant deficient for ATR activation, we show that functional TopBP1 is required in suppressing local dormant origin activation. Our results demonstrate a regulatory role for TopBP1 in the local balancing of replication fork firing within the S phase.
International journal of molecular sciences
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This research was funded by the Academy of Finland grant 251576 to J.E.S., the Finnish Cultural Foundation, North Carelia Regional fund to M.S., and the UFA Grant 3610S30016 by the German Federal Ofﬁce for Radiation Protection as part of the “Kompetenzverbund für Strahlenforschung” to H.P. The Fritz Lipmann Institute is a member of the Science Association “Gottfried Wilhelm Leibniz” (WGL) and ﬁnancially supported by the Federal Government of Germany and the State of Thuringia. Funding for open access charge: Leibniz Insitute on Aging—Fritz Lipmann Institute.
|Academy of Finland Grant Number:||
251576 (Academy of Finland Funding decision)
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).