TOF1 Tof1p [Saccharomyces cerevisiae S288C] - Gene

Summary

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Official Symbol: TOF1
Official Full Name: Tof1p
Primary source: SGD:S000005217
Locus tag: YNL273W
See related: AllianceGenome:SGD:S000005217; FungiDB:YNL273W; VEuPathDB:YNL273W
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Saccharomyces cerevisiae S288C (strain: S288C)
Lineage: Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces
Summary: Predicted to enable DNA binding activity. Involved in DNA metabolic process; DNA replication checkpoint signaling; and mitotic sister chromatid cohesion. Acts upstream of or within replication fork processing. Located in cytosol and nuclear replication fork. Part of replication fork protection complex. Human ortholog(s) of this gene implicated in advanced sleep phase syndrome and alcohol use disorder. Orthologous to human TIMELESS (timeless circadian regulator). [provided by Alliance of Genome Resources, Dec 2024]
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Genomic context

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See TOF1 in Genome Data Viewer

Location:: chromosome: XIV

Exon count:: 1

Sequence:: Chromosome: XIV; NC_001146.8 (122883..126599)

Chromosome XIV - NC_001146.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001146.8

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Separable functions of Tof1/Timeless in intra-S-checkpoint signalling, replisome stability and DNA topological stress.
Title: Separable functions of Tof1/Timeless in intra-S-checkpoint signalling, replisome stability and DNA topological stress.
Results suggest that the Tof1 replicative function exerts its protective role when fork stalling is severe enough to require extra stabilization, such as at long expanded CAG repeats.
Title: Mrc1 and Tof1 prevent fragility and instability at long CAG repeats by their fork stabilizing function.
Phosphorylation regulates the recruitment and retention of Tof1-Csm3 by the replisome and that this complex antagonizes the Rrm3 helicase, thereby promoting replication fork arrest.
Title: Phosphorylation of CMG helicase and Tof1 is required for programmed fork arrest.
although fork rotation and precatenation facilitate unwinding in hard-to-replicate contexts, they intrinsically disrupt normal chromosome duplication and are therefore restricted by Timeless/Tipin
Title: Fork rotation and DNA precatenation are restricted during DNA replication to prevent chromosomal instability.
Tof1, Mrc1 and Csm3 complex, inhibits CAG.CTG repeat instability.
Title: Mrc1, Tof1 and Csm3 inhibit CAG.CTG repeat instability by at least two mechanisms.
Authors show that minisatellite length expansions are controlled by the products of the CSM3 and TOF1 genes, while contractions are controlled by MRC1.
Title: The role of CSM3, MRC1, and TOF1 in minisatellite stability and large loop DNA repair during meiosis in yeast.
Data show that that ISC1 controls cell morphology in combination with checkpoint regulators Swe1, Cdk1(CDC28), MRC1, TOF1, CSM3, RAD9 and Rad53.
Title: Cellular morphogenesis under stress is influenced by the sphingolipid pathway gene ISC1 and DNA integrity checkpoint genes in Saccharomyces cerevisiae.
Functional Tof1 protein, a replication fork-stabilizing protein, precludes expansions of various unstable repeats.
Title: Expansions, contractions, and fragility of the spinocerebellar ataxia type 10 pentanucleotide repeat in yeast.
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.
Title: 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.
Csm3, Tof1, and Mrc1 form a heterotrimeric mediator complex that associates with DNA replication forks
Title: Csm3, Tof1, and Mrc1 form a heterotrimeric mediator complex that associates with DNA replication forks.

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

Orthologs from OrthoDB

Gene Ontology Provided by SGD

Function	Evidence Code	Pubs
enables DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables molecular_function	ND No biological Data available more info

Process	Evidence Code	Pubs
involved_in DNA repair	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA repair	IEA Inferred from Electronic Annotation more info
involved_in DNA repair	IGI Inferred from Genetic Interaction more info	PubMed
involved_in DNA repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA replication checkpoint signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA replication checkpoint signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in maintenance of DNA repeat elements	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in meiotic cell cycle	IEA Inferred from Electronic Annotation more info
involved_in mitotic sister chromatid cohesion	IGI Inferred from Genetic Interaction more info	PubMed
involved_in mitotic sister chromatid cohesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA replication	IEA Inferred from Electronic Annotation more info
involved_in replication fork arrest	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within replication fork arrest	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in replication fork arrest	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within replication fork processing	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear replication fork	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
part_of replication fork protection complex	IBA Inferred from Biological aspect of Ancestor more info
part_of replication fork protection complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: Tof1p

NP_014126.1

Subunit of a replication-pausing checkpoint complex; Tof1p-Mrc1p-Csm3p acts at the stalled replication fork to promote sister chromatid cohesion after DNA damage, facilitating gap repair of damaged DNA; interacts with the MCM helicase; relocalizes to the cytosol in response to hypoxia