Disease relevance of FOB1

• Subsequently, the catalytic domain of HIV-1 integrase was used as a template to build a reliable three-dimensional model of Fob1p [1].

High impact information on FOB1

• It is known that mutations in gene SIR2 increase and those in FOB1 decrease recombination within rDNA repeats as assayed by marker loss or extrachromosomal rDNA circle formation [2].
• 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 contribute to rDNA fragility and genome instability [3].
• We find that Net1 and Sir2 are physically associated with Fob1 and subunits of RNA polymerase I. Together with the localization data, these results suggest the existence of two distinct modes for the recruitment of the RENT complex to rDNA and reveal a role for Fob1 in rDNA silencing and in the recruitment of the RENT complex [4].
• In cells lacking Fob1, silencing and the association of RENT subunits are abolished specifically at NTS1, while silencing and association at the Pol I promoter region are unaffected or increased [4].
• FOB1 was shown previously to be required for replication fork blocking (RFB) activity at RFB site in rDNA and for recombination hot-spot (HOT1) activity [5].

Biological context of FOB1

• FOB1 showed a gene dosage effect on not only the amounts of both recombinants, but also on the copy number of the repeat [6].
• In addition, FOB1 may also play a role in the copy number regulation of rDNA tandem repeats [6].
• Orientation of the RFB sequence in its inactive course or its abolition by FOB1 deletion avoided plasmid integration in sir2 mutant cells, indicating that stalling of the forks in the plasmid context was required for recombination to take place [7].
• FOB1 is required for recombination hot spot (HOT1) activity, which also requires the enhancer region, and for recombination within rDNA repeats [8].
• These results indicate that FOB1 plays a novel role in preventing repeat contraction by regulating condensin association and suggest a link between replication termination and chromosome condensation and segregation [9].

Anatomical context of FOB1

• Deletion of FOB1 and overexpression of SIR2 have been previously found to increase life span by reducing the levels of toxic rDNA circles in aged mother cells [10].
• The rapid-aging phenotype of sip2 Delta cells is fully rescued by blocking recombination at rDNA loci with a fob1 Delta allele; rescue is not accompanied by amelioration of an age-associated shift toward gluconeogenesis and glucose storage [11].

Associations of FOB1 with chemical compounds

• However, even in cells lacking both Sir2 and the replication fork block protein Fob1, nicotinamide partially prevents life span extension by CR [12].

Physical interactions of FOB1

• Finally, we show that Spo12 phosphorylation is cell cycle regulated and affects its binding to Fob1 [13].

Co-localisations of FOB1

• Hmo1 co-localizes with Fob1, a known rDNA-binding protein, defining a narrow territory adjacent to the nucleoplasm that could delineate the rDNA nucleolar domain [14].

Regulatory relationships of FOB1

• The short life span of a sir2 mutant also reveals a direct failure to repress recombination generated by the Fob1p-mediated replication block in the rDNA [15].

Other interactions of FOB1

• FOB1, which is known to be required for ERC formation, and RTG2 were found to be in converging pathways for ERC production [16].
• However, unlike the RAD52 gene, the FOB1 gene was not involved in homologous recombination in a non-rDNA locus [6].
• Either deletion of FOB1, which suppresses fork blocking and certain types of rDNA recombination, or an increase in SIR2 gene dosage, which suppresses rDNA recombination, reduces the number of forks persisting at the RFB [17].
• Conversely, high levels of FOB1 delay the release of Cdc14 from the nucleolus [13].
• FOB1 affects DNA topoisomerase I in vivo cleavages in the enhancer region of the Saccharomyces cerevisiae ribosomal DNA locus [18].

Analytical, diagnostic and therapeutic context of FOB1

• This study documents the detection of fork collision in an fob1 derivative with reduced rDNA copy number (approximately 20) using two-dimensional agarose gel electrophoresis [19].
• Here, I show by using chromatin immunoprecipitation, gel shift, footprinting, and atomic force microscopy assays that Fob1p directly binds to the RFB [20].

References