Alternative titles; symbols
HGNC Approved Gene Symbol: HUS1
Cytogenetic location: 7p12.3 Genomic coordinates (GRCh38): 7:47,963,288-47,979,615 (from NCBI)
The S. pombe 'checkpoint rad' genes hus1, rad1 (603153), rad3, rad9 (603761), rad17 (603139), and rad26 are essential for both the incomplete DNA replication (S-M) and DNA damage checkpoints. An early step in the DNA damage checkpoint response appears to involve activation of the rad3 phosphatidylinositol 3-kinase-related (PIK-R) checkpoint kinase (see AT; 607585) by the other 5 checkpoint rad gene products. Kostrub et al. (1998) found that the fission yeast hus1 and rad1 proteins form a stable complex, and that the formation of this complex is dependent on rad9, suggesting that these 3 proteins may exist in a discrete complex in the absence of checkpoint activation. Hus1 is phosphorylated in response to DNA damage, and this phosphorylation requires rad3 and the other checkpoint rad genes. By searching EST databases, Kostrub et al. (1998) and Dean et al. (1998) each identified mouse and human cDNAs encoding hus1 homologs. Kostrub et al. (1998) reported that the predicted 281-amino acid human protein shares 30% and 86% identity with S. pombe hus1 and mouse Hus1, respectively. However, neither mammalian gene complemented a fission yeast hus1 mutation.
AU-rich elements (AREs) are cis-acting sequences typically found in 3-prime untranslated regions of many labile mRNAs. AREs either mediate rapid degradation of mRNA or inhibit its translation. Dominguez et al. (1998) identified EE2-16C, a HUS1 cDNA, among a collection of ARE-containing mRNAs.
Volkmer and Karnitz (1999) demonstrated that the human RAD1 and HUS1 proteins associate in a complex that interacts with a highly modified form of RAD9. They concluded that these 3 proteins are central components of a DNA damage-responsive protein complex in human cells.
By fluorescence in situ hybridization and by radiation hybrid analysis, Dean et al. (1998) mapped the HUS1 gene to 7p13-p12.
Dean, F. B., Lian, L., O'Donnell, M. cDNA cloning and gene mapping of human homologs for Schizosaccharomyces pombe rad17, rad1, and hus1 and cloning of homologs from mouse, Caenorhabditis elegans, and Drosophila melanogaster. Genomics 54: 424-436, 1998. [PubMed: 9878245] [Full Text: https://doi.org/10.1006/geno.1998.5587]
Dominguez, O., Ashhab, Y., Sabater, L., Belloso, E., Caro, P., Pujol-Borrell, R. Cloning of ARE-containing genes by AU-motif-directed display. Genomics 54: 278-286, 1998. [PubMed: 9828130] [Full Text: https://doi.org/10.1006/geno.1998.5548]
Kostrub, C. F., Knudsen, K., Subramani, S., Enoch, T. Hus1p, a conserved fission yeast checkpoint protein, interacts with Rad1p and is phosphorylated in response to DNA damage. EMBO J. 17: 2055-2066, 1998. [PubMed: 9524127] [Full Text: https://doi.org/10.1093/emboj/17.7.2055]
Volkmer, E., Karnitz, L. M. Human homologs of Schizosaccharomyces pombe Rad1, Hus1, and Rad9 form a DNA damage-responsive protein complex. J. Biol. Chem. 274: 567-570, 1999. [PubMed: 9872989] [Full Text: https://doi.org/10.1074/jbc.274.2.567]