TOF1

Summary

Gene Symbol: TOF1
Description: Tof1p
Alias: Tof1p
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Putnam C, Hayes T, Kolodner R. Post-replication repair suppresses duplication-mediated genome instability. PLoS Genet. 2010;6:e1000933 pubmed publisher
    ..Our analysis is consistent with models in which PRR prevents replication damage from becoming double strand breaks (DSBs) and/or regulates the activity of HR on DSBs. ..
  2. Calzada A, Hodgson B, Kanemaki M, Bueno A, Labib K. Molecular anatomy and regulation of a stable replisome at a paused eukaryotic DNA replication fork. Genes Dev. 2005;19:1905-19 pubmed
    ..The budding yeast proteins Mrc1 and Tof1 associate with the putative MCM-Cdc45 helicase and limit progression of the replisome when nucleotides are depleted,..
  3. Katou Y, Kanoh Y, Bando M, Noguchi H, Tanaka H, Ashikari T, et al. S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex. Nature. 2003;424:1078-83 pubmed
    ..Here we demonstrate that the checkpoint regulatory proteins Tof1 and Mrc1 interact directly with the DNA replication machinery in Saccharomyces cerevisiae...
  4. Tourrière H, Versini G, Cordon Preciado V, Alabert C, Pasero P. Mrc1 and Tof1 promote replication fork progression and recovery independently of Rad53. Mol Cell. 2005;19:699-706 pubmed
    The yeast checkpoint factors Mrc1p and Tof1p travel with the replication fork and mediate the activation of the Rad53p kinase in response to a replication stress...
  5. Komata M, Bando M, Araki H, Shirahige K. The direct binding of Mrc1, a checkpoint mediator, to Mcm6, a replication helicase, is essential for the replication checkpoint against methyl methanesulfonate-induced stress. Mol Cell Biol. 2009;29:5008-19 pubmed publisher
    ..These results strongly suggest for the first time that an Mcm helicase acts as a checkpoint sensor for methyl methanesulfonate-induced DNA damage through direct binding to the replication checkpoint mediator Mrc1. ..
  6. Thaminy S, Newcomb B, Kim J, Gatbonton T, Foss E, Simon J, et al. Hst3 is regulated by Mec1-dependent proteolysis and controls the S phase checkpoint and sister chromatid cohesion by deacetylating histone H3 at lysine 56. J Biol Chem. 2007;282:37805-14 pubmed
    ..Both S phase checkpoint and SCC defects are phenocopied by H3K56 point mutants. Our findings demonstrate that Hst3-regulated H3K56 acetylation safeguards genome stability by controlling the S phase DNA damage response and promoting SCC. ..
  7. Bando M, Katou Y, Komata M, Tanaka H, Itoh T, Sutani T, et al. Csm3, Tof1, and Mrc1 form a heterotrimeric mediator complex that associates with DNA replication forks. J Biol Chem. 2009;284:34355-65 pubmed publisher
    Mrc1 (mediator of replication checkpoint), Tof1 (topoisomerase I interacting factor), and Csm3 (chromosome segregation in meiosis) are checkpoint-mediator proteins that function during DNA replication and activate the effector kinase ..
  8. Tanaka H, Katou Y, Yagura M, Saitoh K, Itoh T, Araki H, et al. Ctf4 coordinates the progression of helicase and DNA polymerase alpha. Genes Cells. 2009;14:807-20 pubmed publisher
    ..The same interaction was not affected in the absence of the replication checkpoint mediators Tof1 or Mrc1...
  9. Voineagu I, Narayanan V, Lobachev K, Mirkin S. Replication stalling at unstable inverted repeats: interplay between DNA hairpins and fork stabilizing proteins. Proc Natl Acad Sci U S A. 2008;105:9936-41 pubmed publisher
    ..Finally, we report that yeast fork-stabilizing proteins, Tof1 and Mrc1, are required to counteract repeat-mediated replication stalling...

More Information

Publications45

  1. Xu H, Boone C, Brown G. Genetic dissection of parallel sister-chromatid cohesion pathways. Genetics. 2007;176:1417-29 pubmed
    ..These data defined two cohesion pathways, one containing CSM3, TOF1, CTF4, and CHL1, and the second containing MRC1, CTF18, CTF8, and DCC1...
  2. Mayer M, Pot I, Chang M, Xu H, Aneliunas V, Kwok T, et al. Identification of protein complexes required for efficient sister chromatid cohesion. Mol Biol Cell. 2004;15:1736-45 pubmed
    ..complexes identified a physical association between Kar3p and Vik1p and an interaction between Csm3p and Tof1p that we confirmed by coimmunoprecipitation from cell extracts...
  3. Fong C, Arumugam A, Koepp D. The Saccharomyces cerevisiae F-box protein Dia2 is a mediator of S-phase checkpoint recovery from DNA damage. Genetics. 2013;193:483-99 pubmed publisher
    ..We propose a model in which Dia2 mediates Mrc1 degradation to help cells resume the cell cycle during recovery from MMS-induced DNA damage in S-phase. ..
  4. Bastia D, Srivastava P, Zaman S, Choudhury M, Mohanty B, Bacal J, et al. Phosphorylation of CMG helicase and Tof1 is required for programmed fork arrest. Proc Natl Acad Sci U S A. 2016;113:E3639-48 pubmed publisher
    ..However, a general mechanism of PFA has remained elusive. We previously showed that the Tof1-Csm3 fork protection complex is essential for PFA by antagonizing the Rrm3 helicase that displaces nonhistone ..
  5. Che J, Smith S, Kim Y, Shim E, Myung K, Lee S. Hyper-Acetylation of Histone H3K56 Limits Break-Induced Replication by Inhibiting Extensive Repair Synthesis. PLoS Genet. 2015;11:e1004990 pubmed publisher
    ..Our studies suggest that acetylation of H3K56 limits extensive repair synthesis and interferes with efficient fork progression in BIR. ..
  6. Reha Krantz L, Siddique M, Murphy K, Tam A, O Carroll M, Lou S, et al. Drug-sensitive DNA polymerase ? reveals a role for mismatch repair in checkpoint activation in yeast. Genetics. 2011;189:1211-24 pubmed publisher
  7. Chang M, Bellaoui M, Zhang C, Desai R, Morozov P, Delgado Cruzata L, et al. RMI1/NCE4, a suppressor of genome instability, encodes a member of the RecQ helicase/Topo III complex. EMBO J. 2005;24:2024-33 pubmed
    ..In addition, rmi1Delta strains fail to fully activate Rad53 upon exposure to DNA-damaging agents, suggesting that Rmi1 is also an important part of the Rad53-dependent DNA damage response. ..
  8. Karumbati A, Wilson T. Abrogation of the Chk1-Pds1 checkpoint leads to tolerance of persistent single-strand breaks in Saccharomyces cerevisiae. Genetics. 2005;169:1833-44 pubmed
    ..We propose a model in which recombinational repair during S phase coupled with failure of the metaphase-anaphase checkpoint allows for tolerance of persistent single-strand breaks at the expense of genome stability. ..
  9. Foss E. Tof1p regulates DNA damage responses during S phase in Saccharomyces cerevisiae. Genetics. 2001;157:567-77 pubmed
    ..I suggest a model in which Tof1p functions to link Mec1p with Rad53p.
  10. Putnam C, Pallis K, Hayes T, Kolodner R. DNA repair pathway selection caused by defects in TEL1, SAE2, and de novo telomere addition generates specific chromosomal rearrangement signatures. PLoS Genet. 2014;10:e1004277 pubmed publisher
    ..L while retaining a chrV L telomeric hph marker was significantly higher in tel1?, sae2?, rad53? sml1?, and mrc1? tof1? mutants...
  11. Naylor M, Li J, Osborn A, Elledge S. Mrc1 phosphorylation in response to DNA replication stress is required for Mec1 accumulation at the stalled fork. Proc Natl Acad Sci U S A. 2009;106:12765-70 pubmed publisher
    ..Together these results reveal new insight into how Mrc1 facilitates checkpoint signal amplification at stalled replication forks. ..
  12. Redon C, Pilch D, Bonner W. 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. Genetics. 2006;172:67-76 pubmed
    ..We now report that efficient repair also requires proteins involved in chromatid cohesion: Csm3; Tof1; Mrc1, and Dcc1. Epistasis analysis defined several pathways involving these proteins...
  13. Tripathi K, Matmati N, Zheng W, Hannun Y, Mohanty B. Cellular morphogenesis under stress is influenced by the sphingolipid pathway gene ISC1 and DNA integrity checkpoint genes in Saccharomyces cerevisiae. Genetics. 2011;189:533-47 pubmed publisher
    ..That is, yeast carrying deletions of both ISC1 and a replication checkpoint mediator gene including MRC1, TOF1, or CSM3 display basal morphological defects, which increase following HU treatment...
  14. Leclere A, Yang J, Kirkpatrick D. The role of CSM3, MRC1, and TOF1 in minisatellite stability and large loop DNA repair during meiosis in yeast. Fungal Genet Biol. 2013;50:33-43 pubmed publisher
    ..Here we show that minisatellite length expansions are controlled by the products of the CSM3 and TOF1 genes, while contractions are controlled by MRC1...
  15. Bairwa N, Mohanty B, Stamenova R, Curcio M, Bastia D. The intra-S phase checkpoint protein Tof1 collaborates with the helicase Rrm3 and the F-box protein Dia2 to maintain genome stability in Saccharomyces cerevisiae. J Biol Chem. 2011;286:2445-54 pubmed publisher
    The intra-S phase checkpoint protein complex Tof1/Csm3 of Saccharomyces cerevisiae antagonizes Rrm3 helicase to modulate replication fork arrest not only at the replication termini of rDNA but also at strong nonhistone protein binding ..
  16. Li X, Tye B. Ploidy dictates repair pathway choice under DNA replication stress. Genetics. 2011;187:1031-40 pubmed publisher
    ..In response to replication stress, early events associated with ploidy dictate the repair pathway choice. This study uncovers a fundamental difference between haplophase and diplophase in the maintenance of genome integrity. ..
  17. Razidlo D, Lahue R. Mrc1, Tof1 and Csm3 inhibit CAG.CTG repeat instability by at least two mechanisms. DNA Repair (Amst). 2008;7:633-40 pubmed publisher
    ..Genetic analysis showed that Mrc1, along with Tof1 and Csm3, inhibits instability in two distinct ways...
  18. Murakami H, Keeney S. Temporospatial coordination of meiotic DNA replication and recombination via DDK recruitment to replisomes. Cell. 2014;158:861-873 pubmed publisher
    ..We now show that, in yeast, the replisome-associated components Tof1 and Csm3 physically associate with the Dbf4-dependent Cdc7 kinase (DDK) and recruit it to the replisome, where it ..
  19. Hodgson B, Calzada A, Labib K. Mrc1 and Tof1 regulate DNA replication forks in different ways during normal S phase. Mol Biol Cell. 2007;18:3894-902 pubmed
    The Mrc1 and Tof1 proteins are conserved throughout evolution, and in budding yeast they are known to associate with the MCM helicase and regulate the progression of DNA replication forks...
  20. Schalbetter S, Mansoubi S, Chambers A, Downs J, Baxter J. Fork rotation and DNA precatenation are restricted during DNA replication to prevent chromosomal instability. Proc Natl Acad Sci U S A. 2015;112:E4565-70 pubmed publisher
    ..However, generally, fork rotation and precatenation are actively inhibited by Timeless/Tof1 and Tipin/Csm3...
  21. O Neill B, Hanway D, Winzeler E, Romesberg F. Coordinated functions of WSS1, PSY2 and TOF1 in the DNA damage response. Nucleic Acids Res. 2004;32:6519-30 pubmed
    ..A yeast two-hybrid screen identified a potential physical interaction between Wss1 and both Psy2 and Tof1. Genetic interactions were also detected between PSY2 and TOF1, as well as between each gene and RAD52 and SRS2, ..
  22. Cherng N, Shishkin A, Schlager L, Tuck R, Sloan L, Matera R, et al. Expansions, contractions, and fragility of the spinocerebellar ataxia type 10 pentanucleotide repeat in yeast. Proc Natl Acad Sci U S A. 2011;108:2843-8 pubmed publisher
    ..A first round of genetic analysis showed that a functional TOF1 gene precludes, whereas a functional RAD5 gene promotes, expansions of the (ATTCT)(n) repeat...
  23. Ohuchi T, Seki M, Kugou K, Tada S, Ohta K, Enomoto T. Accumulation of sumoylated Rad52 in checkpoint mutants perturbed in DNA replication. DNA Repair (Amst). 2009;8:690-6 pubmed publisher
    ..Double mutation of RAD51 and RAD53 exhibited the similar levels of Rad52 sumoylation to RAD53 single mutation. The significance and regulation mechanism of Rad52 sumoylation by checkpoint pathways will be discussed. ..
  24. Tripathi K, Matmati N, Zzaman S, Westwater C, Mohanty B. Nicotinamide induces Fob1-dependent plasmid integration into chromosome XII in Saccharomyces cerevisiae. FEMS Yeast Res. 2012;12:949-57 pubmed publisher
    ..This study suggests that NAD metabolism and intracellular NAM concentrations are important in Fob1-mediated rDNA recombination. ..
  25. Keogh M, Kim J, Downey M, Fillingham J, Chowdhury D, Harrison J, et al. A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature. 2006;439:497-501 pubmed
    ..The dephosphorylation of gammaH2AX by the HTP-C is necessary for efficient recovery from the DNA damage checkpoint. ..
  26. Borges V, Smith D, Whitehouse I, Uhlmann F. An Eco1-independent sister chromatid cohesion establishment pathway in S. cerevisiae. Chromosoma. 2013;122:121-34 pubmed publisher
    ..In addition to Eco1, several other factors contribute to cohesion establishment, including Ctf4, Ctf18, Tof1, Csm3, Chl1 and Mrc1, but little is known about their roles...
  27. Chin J, Bashkirov V, Heyer W, Romesberg F. Esc4/Rtt107 and the control of recombination during replication. DNA Repair (Amst). 2006;5:618-28 pubmed
    ..Similar behavior is also observed in the absence of damage when either of the S-phase checkpoint proteins, Tof1 or Mrc1, is deleted...
  28. Mohanty B, Bairwa N, Bastia D. Contrasting roles of checkpoint proteins as recombination modulators at Fob1-Ter complexes with or without fork arrest. Eukaryot Cell. 2009;8:487-95 pubmed publisher
    ..The checkpoint adapter proteins Tof1 and Csm3 either positively or negatively controlled recombination depending on whether it was provoked by polar ..
  29. Uzunova S, Zarkov A, Ivanova A, Stoynov S, Nedelcheva Veleva M. The subunits of the S-phase checkpoint complex Mrc1/Tof1/Csm3: dynamics and interdependence. Cell Div. 2014;9:4 pubmed publisher
    ..The S. cerevisiae complex Tof1/Csm3/Mrc1 acts to restrain the replicative MCM helicase when DNA synthesis is prohibited...
  30. Grandin N, Charbonneau M. Mrc1, a non-essential DNA replication protein, is required for telomere end protection following loss of capping by Cdc13, Yku or telomerase. Mol Genet Genomics. 2007;277:685-99 pubmed
    ..Combinations between the cdc13-1 mutation and deletion of either TOF1 or PSY2, coding for proteins physically interacting with Mrc1, also resulted in a synthetic growth defect...
  31. Park H, Sternglanz R. Identification and characterization of the genes for two topoisomerase I-interacting proteins from Saccharomyces cerevisiae. Yeast. 1999;15:35-41 pubmed
    ..Two new genes were found and named TOF1 and TOF2. The Tof1 protein has 1238 amino acids and no obvious homologues in databases...
  32. Alzu A, Bermejo R, Begnis M, Lucca C, Piccini D, Carotenuto W, et al. Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes. Cell. 2012;151:835-846 pubmed publisher
  33. Mohanty B, Bairwa N, Bastia D. The Tof1p-Csm3p protein complex counteracts the Rrm3p helicase to control replication termination of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2006;103:897-902 pubmed
    ..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")..
  34. Menolfi D, Delamarre A, Lengronne A, Pasero P, Branzei D. Essential Roles of the Smc5/6 Complex in Replication through Natural Pausing Sites and Endogenous DNA Damage Tolerance. Mol Cell. 2015;60:835-46 pubmed publisher
    ..chromosome fragility and toxic recombination instigated by prolonged pausing and the fork protection complex, Tof1-Csm3...
  35. Nedelcheva M, Roguev A, Dolapchiev L, Shevchenko A, Taskov H, Shevchenko A, et al. Uncoupling of unwinding from DNA synthesis implies regulation of MCM helicase by Tof1/Mrc1/Csm3 checkpoint complex. J Mol Biol. 2005;347:509-21 pubmed
    ..In concordance with this suggestion, we found that the Tof1/Csm3/Mrc1 checkpoint complex interacts directly with the MCM helicase during both replication fork progression and ..
  36. Au T, Rodriguez J, Vincent J, Tsukiyama T. ATP-dependent chromatin remodeling factors tune S phase checkpoint activity. Mol Cell Biol. 2011;31:4454-63 pubmed publisher
    ..Based on these results, we propose that Isw2 and Ino80 are targeted to stalled replication forks via RPA and directly control the amplitude of S phase checkpoint activity and the subsequent deactivation process. ..