Gene Symbol: FOB1
Description: replication fork barrier binding protein FOB1
Alias: HRM1, replication fork barrier binding protein FOB1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Smith D, Li C, Matecic M, Maqani N, Bryk M, Smith J. Calorie restriction effects on silencing and recombination at the yeast rDNA. Aging Cell. 2009;8:633-42 pubmed publisher
  2. Defossez P, Prusty R, Kaeberlein M, Lin S, Ferrigno P, Silver P, et al. Elimination of replication block protein Fob1 extends the life span of yeast mother cells. Mol Cell. 1999;3:447-55 pubmed
    ..We show here that mutation of the FOB1 gene slows the generation of these circles and thus extends life span...
  3. Machin F, Torres Rosell J, De Piccoli G, Carballo J, Cha R, Jarmuz A, et al. Transcription of ribosomal genes can cause nondisjunction. J Cell Biol. 2006;173:893-903 pubmed
    ..In addition, our study uncovers an unexpected role for the replication barrier protein Fob1 in rDNA segregation that is independent of Cdc14...
  4. Stegmeier F, Huang J, Rahal R, Zmolik J, Moazed D, Amon A. The replication fork block protein Fob1 functions as a negative regulator of the FEAR network. Curr Biol. 2004;14:467-80 pubmed
    ..We identify the replication fork block protein Fob1 as a Spo12-interacting factor...
  5. Johzuka K, Terasawa M, Ogawa H, Ogawa T, Horiuchi T. Condensin loaded onto the replication fork barrier site in the rRNA gene repeats during S phase in a FOB1-dependent fashion to prevent contraction of a long repetitive array in Saccharomyces cerevisiae. Mol Cell Biol. 2006;26:2226-36 pubmed
    An average of 200 copies of the rRNA gene (rDNA) is clustered in a long tandem array in Saccharomyces cerevisiae. FOB1 is known to be required for expansion/contraction of the repeats by stimulating recombination, thereby contributing to ..
  6. Kobayashi T. The replication fork barrier site forms a unique structure with Fob1p and inhibits the replication fork. Mol Cell Biol. 2003;23:9178-88 pubmed
    ..The gene FOB1 is required for this RFB activity...
  7. Kaeberlein M, Kirkland K, Fields S, Kennedy B. Genes determining yeast replicative life span in a long-lived genetic background. Mech Ageing Dev. 2005;126:491-504 pubmed
    ..Of the eleven deletion mutations previously reported to increase yeast life span, we find that deletion of FOB1, deletion of SCH9, and deletion of GPA2, GPR1, or HXK2 (three genetic models of calorie restriction) significantly ..
  8. Ha C, Sung M, Huh W. Nsi1 plays a significant role in the silencing of ribosomal DNA in Saccharomyces cerevisiae. Nucleic Acids Res. 2012;40:4892-903 pubmed publisher
    ..In addition, Nsi1 physically interacts with the known rDNA silencing factors Net1, Sir2 and Fob1. The loss of Nsi1 decreases the association of Sir2 with NTS1 and increases histone acetylation at NTS1...
  9. Huang J, Moazed D. Association of the RENT complex with nontranscribed and coding regions of rDNA and a regional requirement for the replication fork block protein Fob1 in rDNA silencing. Genes Dev. 2003;17:2162-76 pubmed
    ..the recombination hotspot and replication fork barrier elements, which have been shown previously to require the Fob1 protein for their activities...

More Information


  1. Kaeberlein M, Kirkland K, Fields S, Kennedy B. Sir2-independent life span extension by calorie restriction in yeast. PLoS Biol. 2004;2:E296 pubmed
    ..Deletion of FOB1 and overexpression of SIR2 have been previously found to increase life span by reducing the levels of toxic rDNA ..
  2. Kobayashi T, Horiuchi T. A yeast gene product, Fob1 protein, required for both replication fork blocking and recombinational hotspot activities. Genes Cells. 1996;1:465-74 pubmed
    ..Genetic analysis of the mutants reveals that a single mutation, named fob1 (fork blocking less), is responsible for the defects in both abilities...
  3. Mohanty B, Bastia D. Binding of the replication terminator protein Fob1p to the Ter sites of yeast causes polar fork arrest. J Biol Chem. 2004;279:1932-41 pubmed
    ..First, a mutant of FOB1, L104S, that significantly reduced the binding of the mutant form of the protein to the tandem Ter sites, also ..
  4. Choudhury M, Zaman S, Jiang J, Jazwinski S, Bastia D. Mechanism of regulation of 'chromosome kissing' induced by Fob1 and its physiological significance. Genes Dev. 2015;29:1188-201 pubmed publisher
    ..Here, we show that the replication terminator protein Fob1 of Saccharomyces cerevisiae promoted chromosome kissing that initiated rDNA recombination and controlled the ..
  5. Saka K, Takahashi A, Sasaki M, Kobayashi T. More than 10% of yeast genes are related to genome stability and influence cellular senescence via rDNA maintenance. Nucleic Acids Res. 2016;44:4211-21 pubmed publisher
  6. Ide S, Saka K, Kobayashi T. Rtt109 prevents hyper-amplification of ribosomal RNA genes through histone modification in budding yeast. PLoS Genet. 2013;9:e1003410 pubmed publisher
    ..We propose that, in the rtt109 mutant, rDNA hyper-amplification is caused by uncontrolled rolling-circle-type replication. ..
  7. Chen X, Meng F, Zhou J. Telomere recombination accelerates cellular aging in Saccharomyces cerevisiae. PLoS Genet. 2009;5:e1000535 pubmed publisher
    ..These results suggest that telomere recombination accelerates cellular aging in telomerase-null type II survivors and that telomerase is likely a superior telomere maintenance pathway in sustaining yeast replicative life span. ..
  8. Molin M, Yang J, Hanzén S, Toledano M, Labarre J, Nystrom T. Life span extension and H(2)O(2) resistance elicited by caloric restriction require the peroxiredoxin Tsa1 in Saccharomyces cerevisiae. Mol Cell. 2011;43:823-33 pubmed publisher
    ..The data demonstrate that Tsa1 is required to ensure yeast longevity and that CR extends yeast life span, in part, by counteracting age-induced hyperoxidation of this peroxiredoxin. ..
  9. Zaman S, Choudhury M, Jiang J, Srivastava P, Mohanty B, Danielson C, et al. Mechanism of Regulation of Intrachromatid Recombination and Long-Range Chromosome Interactions in Saccharomyces cerevisiae. Mol Cell Biol. 2016;36:1451-63 pubmed publisher
    ..RENT ( RE: gulation of N: ucleolar S: ilencing and T: elophase exit) complex and the replication terminator protein Fob1. The latter binds to its cognate sites, called replication termini (Ter) or replication fork barriers (RFB), that ..
  10. Bairwa N, Zzaman S, Mohanty B, Bastia D. Replication fork arrest and rDNA silencing are two independent and separable functions of the replication terminator protein Fob1 of Saccharomyces cerevisiae. J Biol Chem. 2010;285:12612-9 pubmed publisher
    The replication terminator protein Fob1 of Saccharomyces cerevisiae is multifunctional, and it not only promotes polar replication fork arrest at the tandem Ter sites located in the intergenic spacer region of rDNA but also loads the NAD-..
  11. Mundbjerg K, Jørgensen S, Fredsøe J, Nielsen I, Pedersen J, Bentsen I, et al. Top2 and Sgs1-Top3 Act Redundantly to Ensure rDNA Replication Termination. PLoS Genet. 2015;11:e1005697 pubmed publisher
    ..during replication termination, and consistently, checkpoint activation is dependent on the RFB binding protein, Fob1. In contrast, asymmetric X-structures are formed independent of Fob1 at less strong rDNA replication fork barriers...
  12. Wang R, Solomon M. Identification of She3 as an SCF(Grr1) substrate in budding yeast. PLoS ONE. 2012;7:e48020 pubmed publisher
    ..However, She3 stabilization leads to slower growth compared to wild-type cells in a co-culture assay, demonstrating that the degradation of She3 by Grr1 is required for optimal cell growth. ..
  13. Merker R, Klein H. hpr1Delta affects ribosomal DNA recombination and cell life span in Saccharomyces cerevisiae. Mol Cell Biol. 2002;22:421-9 pubmed
    ..The hpr1Delta mutant acts in a pathway distinct from previously described mutants that reduce life span. ..
  14. Di Felice F, Cioci F, Camilloni G. FOB1 affects DNA topoisomerase I in vivo cleavages in the enhancer region of the Saccharomyces cerevisiae ribosomal DNA locus. Nucleic Acids Res. 2005;33:6327-37 pubmed
    In Saccharomyces cerevisiae the FOB1 gene affects replication fork blocking activity at the replication fork block (RFB) sequences and promotes recombination events within the rDNA cluster...
  15. Moretto F, Sagot I, Daignan Fornier B, Pinson B. A pharmaco-epistasis strategy reveals a new cell size controlling pathway in yeast. Mol Syst Biol. 2013;9:707 pubmed publisher
    ..This study sheds light on a pathway of >50 genes and illustrates how pharmaco-epistasis applied to yeast offers a potent experimental framework to explore complex genotype/phenotype relationships...
  16. Saka K, Ide S, Ganley A, Kobayashi T. Cellular senescence in yeast is regulated by rDNA noncoding transcription. Curr Biol. 2013;23:1794-8 pubmed publisher
    ..The observation of rDNA instability in other organisms, including humans, suggests that this may be a conserved aging pathway. ..
  17. Delaney J, Ahmed U, Chou A, Sim S, Carr D, Murakami C, et al. Stress profiling of longevity mutants identifies Afg3 as a mitochondrial determinant of cytoplasmic mRNA translation and aging. Aging Cell. 2013;12:156-66 pubmed publisher
    ..These data demonstrate an unexpected link between a mitochondrial protease, cytoplasmic mRNA translation, and aging. ..
  18. Oling D, Masoom R, Kvint K. Loss of Ubp3 increases silencing, decreases unequal recombination in rDNA, and shortens the replicative life span in Saccharomyces cerevisiae. Mol Biol Cell. 2014;25:1916-24 pubmed publisher
    ..We discuss the data in view of different models on how silencing and unequal recombination affect replicative life span and the role of Ubp3 in these processes. ..
  19. Peng J, He M, Duan Y, Liu Y, Zhou J. Inhibition of telomere recombination by inactivation of KEOPS subunit Cgi121 promotes cell longevity. PLoS Genet. 2015;11:e1005071 pubmed publisher
    ..Strikingly, inhibition of telomere recombination is able to further slow down the aging process in long-lived fob1Δ cells, in which rDNA recombination is restrained...
  20. Johzuka K, Horiuchi T. The cis element and factors required for condensin recruitment to chromosomes. Mol Cell. 2009;34:26-35 pubmed publisher
    Condensins are required for segregation of rDNA repeats in concert with Fob1, a replication fork block protein binding at the replication fork barrier (RFB) site within rDNA in yeast...
  21. Gillies J, Hickey C, Su D, Wu Z, Peng J, Hochstrasser M. SUMO Pathway Modulation of Regulatory Protein Binding at the Ribosomal DNA Locus in Saccharomyces cerevisiae. Genetics. 2016;202:1377-94 pubmed publisher
    ..b>Fob1, a protein that anchors both Net1 and Tof2 to the replication-fork barrier (RFB) in the rDNA repeats, is sumoylated ..
  22. 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
    In the ribosomal DNA (rDNA) array of Saccharomyces cerevisiae, DNA replication is arrested by the Fob1 protein in a site-specific manner that stimulates homologous recombination...
  23. Bentsen I, Nielsen I, Lisby M, Nielsen H, Gupta S, Mundbjerg K, et al. MRX protects fork integrity at protein-DNA barriers, and its absence causes checkpoint activation dependent on chromatin context. Nucleic Acids Res. 2013;41:3173-89 pubmed publisher
    ..We demonstrate that proper checkpoint signalling within the rDNA is restored on deletion of SIR2. This suggests the surprising and novel concept that chromatin is an important player in checkpoint signalling. ..
  24. Quevedo O, Garcia Luis J, Matos Perdomo E, Aragon L, Machin F. Nondisjunction of a single chromosome leads to breakage and activation of DNA damage checkpoint in G2. PLoS Genet. 2012;8:e1002509 pubmed publisher
    ..Our results demonstrate that, in yeast cells, the Rad9-DNA damage checkpoint plays an important role responding to compromised genome integrity caused by mitotic nondisjunction. ..
  25. Feser J, Truong D, Das C, Carson J, KIEFT J, Harkness T, et al. Elevated histone expression promotes life span extension. Mol Cell. 2010;39:724-35 pubmed publisher
    ..This study indicates that maintenance of the fundamental chromatin structure is critical for slowing down the aging process and reveals that increasing the histone supply extends life span. ..
  26. Buck S, Maqani N, Matecic M, Hontz R, Fine R, Li M, et al. RNA Polymerase I and Fob1 contributions to transcriptional silencing at the yeast rDNA locus. Nucleic Acids Res. 2016;44:6173-84 pubmed publisher
    ..polymerase I (Pol I), and to a pair of DNA replication fork block sites (Ter1 and Ter2) through interaction with Fob1. We utilized a reporter gene (mURA3) integrated adjacent to the leftmost rDNA gene to investigate localized Pol I ..
  27. 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
  28. Lindstrom D, Gottschling D. The mother enrichment program: a genetic system for facile replicative life span analysis in Saccharomyces cerevisiae. Genetics. 2009;183:413-22, 1SI-13SI pubmed publisher
    ..We show that viability of mother cells in liquid culture is regulated by SIR2 and FOB1, two opposing regulators of RLS in yeast...
  29. Lu S, Lee K, Harris B, Xiong B, Bose T, Saraf A, et al. The cohesin acetyltransferase Eco1 coordinates rDNA replication and transcription. EMBO Rep. 2014;15:609-17 pubmed publisher
    ..We show that deleting FOB1--a gene that encodes a replication fork-blocking protein specific for the rDNA region--rescues rRNA production and ..
  30. Menzel J, Malo M, Chan C, Prusinkiewicz M, Arnason T, Harkness T. The anaphase promoting complex regulates yeast lifespan and rDNA stability by targeting Fob1 for degradation. Genetics. 2014;196:693-709 pubmed publisher
    ..Our two-hybrid screen utilizing Apc5 as bait recovered the lifespan determinant Fob1 as prey...
  31. Hoopes L, Budd M, Choe W, Weitao T, Campbell J. Mutations in DNA replication genes reduce yeast life span. Mol Cell Biol. 2002;22:4136-46 pubmed
    ..addition, the life span of dna2 mutants is extended by expression of an additional copy of SIR2 or by deletion of FOB1, which also increase wild-type life span...
  32. Albert B, Léger Silvestre I, Normand C, Ostermaier M, Pérez Fernández J, Panov K, et al. RNA polymerase I-specific subunits promote polymerase clustering to enhance the rRNA gene transcription cycle. J Cell Biol. 2011;192:277-93 pubmed publisher
    ..Together our data suggest that localized rRNA production results in spatially constrained rRNA production, which is instrumental for nucleolar assembly. ..
  33. Jiang J, Stumpferl S, Tiwari A, Qin Q, Rodríguez Quiñones J, Jazwinski S. Identification of the Target of the Retrograde Response that Mediates Replicative Lifespan Extension in Saccharomyces cerevisiae. Genetics. 2016;204:659-673 pubmed
    ..The finding that this gene is PHO84 opens up a new set of questions about the mechanisms involved, as this gene is known to have pleiotropic effects. ..
  34. Cieśla M, Makała E, Płonka M, Bazan R, Gewartowski K, Dziembowski A, et al. Rbs1, a new protein implicated in RNA polymerase III biogenesis in yeast Saccharomyces cerevisiae. Mol Cell Biol. 2015;35:1169-81 pubmed publisher
    ..Additionally, Rbs1 interacts with the Crm1 exportin and shuttles between the cytoplasm and nucleus. We postulate that Rbs1 binds to the Pol III complex or subcomplex and facilitates its translocation to the nucleus. ..
  35. McVey M, Kaeberlein M, Tissenbaum H, Guarente L. The short life span of Saccharomyces cerevisiae sgs1 and srs2 mutants is a composite of normal aging processes and mitotic arrest due to defective recombination. Genetics. 2001;157:1531-42 pubmed
    ..Finally, mutation of RAD1 or RAD50 exacerbates the growth defect of sgs1 srs2 cells, indicating that sgs1 srs2 mutants may utilize single-strand annealing as an alternative repair pathway. ..
  36. Salvi J, Chan J, Szafranski K, Liu T, Wu J, Olsen J, et al. Roles for Pbp1 and caloric restriction in genome and lifespan maintenance via suppression of RNA-DNA hybrids. Dev Cell. 2014;30:177-91 pubmed publisher
    ..Thus, we find roles for Pbp1 in genome maintenance and reveal that caloric restriction counteracts Pbp1 deficiencies by engaging RNaseH and Pif1...
  37. Yoshida K, Bacal J, Desmarais D, Padioleau I, Tsaponina O, Chabes A, et al. The histone deacetylases sir2 and rpd3 act on ribosomal DNA to control the replication program in budding yeast. Mol Cell. 2014;54:691-7 pubmed publisher
    ..Together, these data indicate that HDACs control the replication timing program in budding yeast by modulating the ability of repeated origins to compete with single-copy origins for limiting initiation factors. ..
  38. Torres J, Bessler J, Zakian V. Local chromatin structure at the ribosomal DNA causes replication fork pausing and genome instability in the absence of the S. cerevisiae DNA helicase Rrm3p. Genes Dev. 2004;18:498-503 pubmed
    ..Because rrm3-induced increases in recombination and cell cycle length were only partially suppressed in rrm3 fob1 cells, which still required checkpoint and fork restart activities for viability, non-RFB rrm3-induced defects ..
  39. Easlon E, Tsang F, Skinner C, Wang C, Lin S. The malate-aspartate NADH shuttle components are novel metabolic longevity regulators required for calorie restriction-mediated life span extension in yeast. Genes Dev. 2008;22:931-44 pubmed publisher
    ..Together, these data suggest that CR may extend life span and ameliorate age-associated metabolic diseases by activating components of the NADH shuttles. ..
  40. 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 replication terminator protein Fob1 of Saccharomyces cerevisiae specifically interacts with two tandem Ter sites (replication fork barriers) located in the nontranscribed spacer of ribosomal DNA (rDNA) to cause polar fork arrest...