Disease relevance of HOP1

• HOP1 protein, present in sporulating cells of Saccharomyces cerevisiae and believed to be a component of the synaptonemal complex, has been expressed in Escherichia coli fused to a biotinylated tag protein [1].

High impact information on HOP1

• Most of the Pch2 protein localizes to the nucleolus, where it represses meiotic interhomolog recombination in the ribosomal DNA, apparently by excluding the meiosis-specific Hop1 protein [2].
• Also, joint molecule formation is aberrant in a mutant defective in the HOP1 gene, which encodes a meiotic chromosome structure component [3].
• The HOP1 gene in Saccharomyces cerevisiae is important for meiotic chromosomal pairing, because hop1 diploids fail to form synaptonemal complex during meiosis and are defective in crossing over between, but not within, chromosomes [4].
• Furthermore, the HOP1 protein contains a Cys2/Cys2 zinc finger motif [4].
• Using a screen designed to identify yeast mutants specifically defective in recombination between homologous chromosomes during meiosis, we have obtained new alleles of the meiosis-specific genes, HOP1, RED1, and MEK1 [5].

Biological context of HOP1

• No alleles of RED1 or HOP1 were isolated, consistent with the proposal that these genes may be primarily involved with chromosome pairing and not exchange [6].
• Insertional mutations in the yeast HOP1 gene: evidence for multimeric assembly in meiosis [7].
• The HOP1 gene of Saccharomyces cerevisiae has been shown to play an important role in meiotic synapsis [7].
• Complex patterns of complementation and enhancement of the spore-inviability phenotype indicate that HOP1 functions in a multimeric complex [7].
• Overexpression of REC104 from a 2 mu plasmid was shown to enhance the spore viability of every allele tested, including a hop1 disruption allele [7].

Anatomical context of HOP1

• Once solubilized from bacterial inclusion bodies, the HOP1 fusion protein was purified by using a combination of avidin-affinity chromatography and gel filtration FPLC and refolded [1].

Associations of HOP1 with chemical compounds

• Addition of tetracycline nearly completely repressed activator-dependent transcription from the tetO-HOP1 promoter [8].
• A mutation within this motif that changes a cysteine to serine results in the hop1 phenotype, consistent with the possibility that the HOP1 gene product acts in chromosome synapsis by directly interacting with DNA [4].
• Structural analysis of the Holliday junction using 2-aminopurine fluorescence emission, DNase I footprinting and KMnO(4) probing provide compelling evidence that Hop1 protein binding induces significant distortion at the center of the Holliday junction [9].
• Meiosis-specific yeast Hop1 protein promotes synapsis of double-stranded DNA helices via the formation of guanine quartets [10].

Physical interactions of HOP1

• Red1p, a MEK1-dependent phosphoprotein that physically interacts with Hop1p during meiosis in yeast [11].
• Our data strongly support the idea that RED1 protein is also a component of the synaptonemal complex and further suggest that the RED1 and HOP1 gene products may interact [12].
• These findings suggest that Hop1 acts in meiotic synapsis by binding to sites of double-strand break formation and helping to mediate their processing in the pathway to meiotic recombination [13].
• The Abf1p-binding sites from the early HOP1 and the middle SMK1 promoters are functionally interchangeable, demonstrating that these elements do not play a direct role in their differential transcriptional timing [14].
• Fusion of TBP to a zinc cluster DNA binding domain relieves repression at a HOP1 promoter modified to include the zinc cluster target site [15].

Regulatory relationships of HOP1

• Co-immunoprecipitation experiments demonstrated that the interaction between Hop1p and Red1p is enhanced by the presence of MEK1 [11].
• In addition, the SMK1 MSE can repress vegetative expression in the context of the HOP1 promoter and convert HOP1 from an early to a middle gene [14].

Other interactions of HOP1

• HOP1 and RED1 have been classified as such early genes [16].
• The in situ hybridization procedure revealed defects in meiotic chromatin condensation in mer1, red1 and hop1 strains [17].
• Finally, mutations in either HOP1 or RED1 reduce the number of double-strand breaks observed at the HIS2 meiotic recombination hotspot [16].
• Thus, MEK1-dependent phosphorylation of Red1p facilitates the formation of Hop1p/Red1p hetero-oligomers, thereby enabling the formation of functional AEs [11].
• Mutations in the genes RAD50, SPO11 and HOP1 were introduced individually into this disomic strain using transformation procedures [18].

Analytical, diagnostic and therapeutic context of HOP1

• Affinity-purified antibodies show high binding capacity to HOP1 recombinant protein in immunoblotting experiments, but reduced background compared with crude antiserum or purified IgG fraction [19].
• The HOP1 fusion protein was produced in an insoluble form within the bacteria; once solubilized using a denaturing agent, the protein was purified by avidin monomer affinity chromatography [19].
• In contrast, chromatin immunoprecipitation shows that TATA box-binding protein (TBP)- promoter binding is reduced upon repression of HOP1 [15].
• Electrophoretic gel mobility shift assays with different forms of M13 DNA showed that Hop1 binds more readily to linear duplex DNA and negatively superhelical DNA than to nicked circular duplex DNA and even more weakly to single-stranded DNA [13].
• Electron microscopy revealed that diploids homozygous for hop1 fail to form synaptonemal complex, which normally provides the structural basis for homolog pairing [20].

References