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Separable functions of Tof1/Timeless in intra-S-checkpoint signalling, replisome stability and DNA topological stress
Version 2 2023-06-12, 09:32
Version 1 2023-06-09, 21:51
journal contribution
posted on 2023-06-12, 09:32 authored by Emma Westhorpe, Andrea KeszthelyiAndrea Keszthelyi, Nicola Minchell, David JonesDavid Jones, Jon BaxterJon BaxterThe 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.
Funding
Investigating how replication fork rotation causes chromosomal instability during S phase; G1903; BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL; BB/N007344/1
History
Publication status
- Published
File Version
- Published version
Journal
Nucleic Acids ResearchISSN
0305-1048Publisher
Oxford University PressExternal DOI
Issue
21Volume
48Page range
12169-12187Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2020-10-12First Open Access (FOA) Date
2020-11-12First Compliant Deposit (FCD) Date
2020-10-09Usage metrics
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