Assembly of Slx4 signaling complexes behind DNA replication forks |
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| Authors: | Attila Balint TaeHyung Kim David Gallo Jose Renato Cussiol Francisco M Bastos de Oliveira Askar Yimit Jiongwen Ou Ryuichiro Nakato Alexey Gurevich Katsuhiko Shirahige Marcus B Smolka Zhaolei Zhang Grant W Brown |
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| Institution: | 1. Department of Biochemistry, University of Toronto, Toronto, ON, Canada;2. Donnelly Centre, University of Toronto, Toronto, ON, Canada;3. Department of Computer Science, University of Toronto, Toronto, ON, Canada;4. Department of Molecular Biology and Genetics and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA;5. Institute of Molecular and Cellular Biosciences, Research Center for Epigenetic Disease, University of Tokyo, Tokyo, Japan |
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| Abstract: | Obstructions to replication fork progression, referred to collectively as DNA replication stress, challenge genome stability. In Saccharomyces cerevisiae, cells lacking RTT107 or SLX4 show genome instability and sensitivity to DNA replication stress and are defective in the completion of DNA replication during recovery from replication stress. We demonstrate that Slx4 is recruited to chromatin behind stressed replication forks, in a region that is spatially distinct from that occupied by the replication machinery. Slx4 complex formation is nucleated by Mec1 phosphorylation of histone H2A, which is recognized by the constitutive Slx4 binding partner Rtt107. Slx4 is essential for recruiting the Mec1 activator Dpb11 behind stressed replication forks, and Slx4 complexes are important for full activity of Mec1. We propose that Slx4 complexes promote robust checkpoint signaling by Mec1 by stably recruiting Dpb11 within a discrete domain behind the replication fork, during DNA replication stress. |
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| Keywords: | checkpoint kinase replication stress DNA damage response Dpb11 Slx4 |
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