Separable functions of Tof1/Timeless in intra-S-checkpoint signalling, replisome stability and DNA topological stress

Westhorpe, Rose, Keszthelyi, Andrea, Minchell, Nicola E, Jones, David and Baxter, Jonathan (2020) Separable functions of Tof1/Timeless in intra-S-checkpoint signalling, replisome stability and DNA topological stress. Nucleic Acids Research. pp. 1-19. ISSN 0305-1048

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Abstract

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.

Item Type: Article
Keywords: DNA replication, Replication stress, Timeless, Tof1, DNA checkpoint
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 12 Oct 2020 08:34
Last Modified: 12 Nov 2020 14:30
URI: http://sro.sussex.ac.uk/id/eprint/94282

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