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Gene Review

TOF1  -  Tof1p

Saccharomyces cerevisiae S288c

Synonyms: N0636, Topoisomerase 1-associated factor 1, YNL273W
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High impact information on TOF1

  • Mrc1 and Tof1 promote replication fork progression and recovery independently of Rad53 [1].
  • The results support the notion that Swi1p and Swi3p act at several different protein–DNA complexes in the rDNA spacer regions to arrest replication but that not all fork barriers required their activity to arrest forks [2].
  • Simultaneous deletions of the TOF1 (or CSM3), and the RRM3 genes restored fork arrest by removing both the fork-releasing and fork-protection activities [3].
  • Here we show, by both 2D gel analyses and chromatin immunoprecipitations (ChIP), that there exists a second level of global control mediated by the intra-S-phase checkpoint protein complex of Tof1p and Csm3p that protect stalled forks at Ter sites against the activity of the Rrm3p helicase ("sweepase") [3].
  • Here we report studies of fission yeast Swi1, a Tof1-related protein required for a programmed fork-pausing event necessary for mating type switching [4].
  • Members of this second protein family in yeast (S.c. Tof1p, S.p. Swi1p) have been implicated in DNA synthesis, S-phase-dependent checkpoint activation and chromosome cohesion, three processes coordinated at the level of the replication fork complex [5].

Biological context of TOF1

  • TOF1's contribution to DNA damage response appeared to be restricted to S phase, since TOF1 did not contribute to UV-induced transcription during G1 or to the cdc13-1-induced block to anaphase in G2/M [6].
  • A tof1 mutant was recovered in a screen aimed at identifying genes involved specifically in the S phase branch of the MEC1-dependent DNA damage response pathway [6].
  • We now report that efficient repair also requires proteins involved in chromatid cohesion: Csm3; Tof1; Mrc1, and Dcc1 [7].
  • Here we demonstrate that the checkpoint regulatory proteins Tof1 and Mrc1 interact directly with the DNA replication machinery in Saccharomyces cerevisiae [8].

Associations of TOF1 with chemical compounds


Physical interactions of TOF1

  • Tof1 is known to be involved in stabilizing stalled replication forks and our data suggest that Wss1 and Psy2 similarly function to stabilize or process stalled or collapsed replication forks [9].

Other interactions of TOF1


  1. Mrc1 and Tof1 promote replication fork progression and recovery independently of Rad53. Tourrière, H., Versini, G., Cordón-Preciado, V., Alabert, C., Pasero, P. Mol. Cell (2005) [Pubmed]
  2. swi1- and swi3-dependent and independent replication fork arrest at the ribosomal DNA of Schizosaccharomyces pombe. Krings, G., Bastia, D. Proc. Natl. Acad. Sci. U. S. A. (2004) [Pubmed]
  3. The Tof1p-Csm3p protein complex counteracts the Rrm3p helicase to control replication termination of Saccharomyces cerevisiae. Mohanty, B.K., Bairwa, N.K., Bastia, D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Swi1 prevents replication fork collapse and controls checkpoint kinase Cds1. Noguchi, E., Noguchi, C., Du, L.L., Russell, P. Mol. Cell. Biol. (2003) [Pubmed]
  5. Mammalian TIMELESS and Tipin are Evolutionarily Conserved Replication Fork-associated Factors. Gotter, A.L., Suppa, C., Emanuel, B.S. J. Mol. Biol. (2007) [Pubmed]
  6. Tof1p regulates DNA damage responses during S phase in Saccharomyces cerevisiae. Foss, E.J. Genetics (2001) [Pubmed]
  7. Genetic analysis of Saccharomyces cerevisiae H2A serine 129 mutant suggests a functional relationship between H2A and the sister-chromatid cohesion partners Csm3-Tof1 for the repair of topoisomerase I-induced DNA damage. Redon, C., Pilch, D.R., Bonner, W.M. Genetics (2006) [Pubmed]
  8. S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex. Katou, Y., Kanoh, Y., Bando, M., Noguchi, H., Tanaka, H., Ashikari, T., Sugimoto, K., Shirahige, K. Nature (2003) [Pubmed]
  9. Coordinated functions of WSS1, PSY2 and TOF1 in the DNA damage response. O'Neill, B.M., Hanway, D., Winzeler, E.A., Romesberg, F.E. Nucleic Acids Res. (2004) [Pubmed]
  10. Identification and characterization of the genes for two topoisomerase I-interacting proteins from Saccharomyces cerevisiae. Park, H., Sternglanz, R. Yeast (1999) [Pubmed]
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