High impact information on HMO1

• Hmo1 overexpression suppresses rpa49-Delta mutants lacking Rpa49, a non-essential but conserved subunit of RNA polymerase I corresponding to the animal RNA polymerase I factor PAF53 [1].
• 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 [1].
• Among them is Abf2p, an abundant, high-mobility group protein that is known to function in nucleoid morphology, and in mtDNA transactions [2].
• A close relative of the nuclear, chromosomal high-mobility group protein HMG1 in yeast mitochondria [3].
• Lastly, like mammalian UBF, Hmo1 associates at many locations throughout the rRNA gene locus, and it is important for processing of rRNA in addition to its role in rRNA transcription [4].

Biological context of HMO1

• Taken together, the data indicate that HMO1 is likely to be the homolog of HMG1/2 in higher cells and that it plays an important role in genome maintenance [5].
• HSM2 (HMO1) gene participates in mutagenesis control in yeast Saccharomyces cerevisiae [6].
• HMO1 bends DNA, as measured by DNA cyclization assays, facilitating cyclization of 136-, 105-, and 87-bp DNA, but not 75-bp DNA, and it has a significantly longer residence time on DNA minicircles compared with linear duplex DNA [7].
• Determination of DNA substrate specificity using electrophoretic mobility shift assays shows unexpectedly that the lysine-rich tail does not increase DNA binding affinity but instead is required for DNA bending by full-length HMO1; HMO1-boxBC, lacking the box A domain, also fails to bend DNA [8].
• Amino acid sequence alignment suggests that this protein, Hmo1p, is related to the HMG1/2 class of chromatin-associated proteins [5].

Associations of HMO1 with chemical compounds

• As HMO1-boxAB, lacking only the lysine-rich C-terminal segment, exhibits two melting transitions at 46.0 and 63.3 degrees C, we conclude that the destabilization of the box A domain seen in full-length HMO1 is due primarily to its interaction with the lysine-rich tail [8].
• Determinants of DNA binding and bending by the Saccharomyces cerevisiae high mobility group protein NHP6A that are important for its biological activities. Role of the unique N terminus and putative intercalating methionine [9].

Other interactions of HMO1

• We find that mutations in HMO1, which encodes a high mobility group 1/2 homolog, are synthetically lethal with mutations in the yeast FPR1 gene encoding FKBP12 [10].
• The frequency of UV-induced mutations in hsm2 rev3 was not altered in comparison with single rev3 mutant [6].
• The UV-induced mutation frequency in double hsm2 hsm3 mutant was lower than in the single hsm2 and hsm3 mutants [6].
• These data identify Hmo1 as a genuine RNA polymerase I factor acting synergistically with Rpa49 [1].

Analytical, diagnostic and therapeutic context of HMO1

• Using electrophoretic mobility shift assays, we have shown here that HMO1 binds 26-bp duplex DNA with K(d) = 39.6 +/- 5.0 nm and that its divergent box A domain participates in DNA interactions, albeit with low affinity [7].
• Here we use chromatin immunoprecipitation coupled with microarray analysis to determine the genome-wide association of Hmo1 [4].
• Chromatin immunoprecipitation of epitope-tagged Hmo1 selectively precipitates CAG repeat tracts DNAs that range from 26 to 126 repeat units [11].

References