Separable functions of Tof1/Timeless in intra-S-checkpoint signalling, replisome stability and DNA topological stress.
The highly conserved Tof1/Timeless proteins minimise replication stress and promote normal DNA replication. They are required to mediate the DNA replication checkpoint (DRC), the stable pausing of forks at protein fork blocks, the coupling of DNA helicase and polymerase functions during replication stress (RS) and the preferential resolution of DNA ... topological stress ahead of the fork. Here we demonstrate that the roles of the Saccharomyces cerevisiae Timeless protein Tof1 in DRC signalling and resolution of DNA topological stress require distinct N and C terminal regions of the protein, whereas the other functions of Tof1 are closely linked to the stable interaction between Tof1 and its constitutive binding partner Csm3/Tipin. By separating the role of Tof1 in DRC from fork stabilisation and coupling, we show that Tof1 has distinct activities in checkpoint activation and replisome stability to ensure the viable completion of DNA replication following replication stress.
Mesh Terms:
Cell Cycle Checkpoints, Cell Cycle Proteins, DNA Replication, DNA-Binding Proteins, Gene Expression Regulation, Fungal, Mutation, Plasmids, Protein Binding, Protein Domains, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Cell Cycle Checkpoints, Cell Cycle Proteins, DNA Replication, DNA-Binding Proteins, Gene Expression Regulation, Fungal, Mutation, Plasmids, Protein Binding, Protein Domains, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Nucleic Acids Res
Date: Dec. 02, 2019
PubMed ID: 33166393
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