HCM1/YCR065W Summary Help

Standard Name HCM1
Systematic Name YCR065W
Feature Type ORF, Verified
Description Forkhead transcription factor that drives S-phase specific expression of genes involved in chromosome segregation, spindle dynamics, and budding; suppressor of calmodulin mutants with specific SPB assembly defects; telomere maintenance role (1, 2, 3, 4 and see Summary Paragraph)
Name Description High-Copy suppressor of Calmodulin 1
Chromosomal Location
ChrIII:229310 to 231004 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All HCM1 GO evidence and references
  View Computational GO annotations for HCM1
Molecular Function
Manually curated
High-throughput
Biological Process
Manually curated
Cellular Component
Manually curated
Regulatory Role
Binding motifs
    Regulatory modules predicted: stressResponse (589, 523, 517, 475)
    predicted: cellcycle (359, 275, 257, 227)
    predicted: stressResponse (589, 523, 517, 475)
    predicted: cellcycle (359, 275, 257, 227)
    Resources
    Mutant phenotypes All HCM1 Phenotype evidence and references
    Classical genetics
    null
    overexpression
    Large-scale survey
    null
    Resources
    interactions All HCM1 Interaction evidence and references
    300 total interaction(s) for 169 unique genes/features.
    Physical Interactions
    • Affinity Capture-MS: 7
    • Affinity Capture-RNA: 2
    • Affinity Capture-Western: 2
    • Biochemical Activity: 3
    • Two-hybrid: 2
    Genetic Interactions
    • Dosage Rescue: 6
    • Negative Genetic: 213
    • Phenotypic Enhancement: 5
    • Positive Genetic: 26
    • Synthetic Growth Defect: 19
    • Synthetic Lethality: 11
    • Synthetic Rescue: 4
    Resources
    Expression Summary
    histogram
    Resources
    Protein Information All HCM1 Protein evidence and references
    Localization
    Phosphorylation PhosphoGRID | PhosphoPep Database
    Structure
    Homologs
    sequence information
    ChrIII:229310 to 231004 | ORF Map | GBrowse
    SGD ORF map
    Last Update Coordinates: 2011-02-03 | Sequence: 2000-09-13
    Subfeature details
    Relative
    Coordinates    		 Chromosomal
    Coordinates    		 Most Recent Updates
    Coordinates Sequence
    CDS 1..1695 229310..231004 2011-02-03 2000-09-13
    Retrieve sequences
    Analyze Sequence
    S288C only
    S288C vs. other species
    S288C vs. other strains
    Resources
    External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
    Primary SGDIDS000000661
    SUMMARY PARAGRAPH for HCM1

    HCM1 is a member of the winged-helix/forkhead (FOX) transcription factor gene family that regulates the late S-phase specific expression of genes involved in chromosome segregation (including motor protein, kinetochore component, and sister-chromatid cohesion genes), spindle dynamics, and budding (4, 5). In addition, HCM1 drives the expression of FKH1, FKH2, and NDD1, M-phase specific transcription factors required for the subsequent temporal wave of cell cycle regulated transcription, and two cell cycle specific transcriptional repressors, WHI5 and YHP1 (4).

    HCM1 was originally identified as a high-copy number suppressor of a calmodulin (CMD1) mutant with a specific defect in the assembly of the spindle pole body (SPB) and was later found to regulate the expression of SPC110, a gene that encodes a calmodulin binding protein and SPB component (1, 2). HCM1 mutants display elevated rates of chromosome loss, in keeping with the set of target genes that are up-regulated by this transcription factor (4). HCM1 mutants require an intact spindle checkpoint for viability, as evidenced by their sensitivity to the spindle poison benomyl and also by the synthetic sick or lethal phenotype of the hcm1 mutation in combination with mad1, mad2 or pds1 mutations (6, 7, 8). Based on these results and the G2 delay identified in HCM1 mutant strains it has been proposed that the chromosome segregation defects associated with the mutation activate the spindle checkpoint, and that in the absence of checkpoint components this has deleterious consequences (4).

    The HCM1 gene is cell cycle regulated, with peak expression in the G1 phase of the cell cycle; abundance of Hcm1p reflects a similar periodicity (9, 10, 4). The HCM1 promoter contains binding sites for both MBF (Swi4p-Swi6p) and SBF (Mbp1p-Swi6p), two late G1 transcription factor complexes, and is bound in vivo by both complexes (11, 12, 10, 5). Mutational analysis indicates that HCM1 transcription is subject to redundant positive regulation by both MBF and SBF (13). Hcm1p is also post-translationally regulated and has been identified as an efficient in vitro substrate of Cdc28p-Clb2p complexes (4, 14). Similar genes have been identified in many organisms including S. pombe, C. albicans, mouse, rat and human but to date none have been found that encode for proteins with functions that parallel Hcm1p (4, 15, 16, 17).

    Last updated: 2007-01-25

    References cited on this page View Complete Literature Guide for HCM1
    1) Zhu G, et al.  (1993) A dosage-dependent suppressor of a temperature-sensitive calmodulin mutant encodes a protein related to the fork head family of DNA-binding proteins. Mol Cell Biol 13(3):1779-87
    2) Zhu G and Davis TN  (1998) The fork head transcription factor Hcm1p participates in the regulation of SPC110, which encodes the calmodulin-binding protein in the yeast spindle pole body. Biochim Biophys Acta 1448(2):236-44
    3) Askree SH, et al.  (2004) A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect telomere length. Proc Natl Acad Sci U S A 101(23):8658-63
    4) Pramila T, et al.  (2006) The Forkhead transcription factor Hcm1 regulates chromosome segregation genes and fills the S-phase gap in the transcriptional circuitry of the cell cycle. Genes Dev 20(16):2266-78
    5) Horak CE, et al.  (2002) Complex transcriptional circuitry at the G1/S transition in Saccharomyces cerevisiae. Genes Dev 16(23):3017-33
    6) Sarin S, et al.  (2004) Uncovering novel cell cycle players through the inactivation of securin in budding yeast. Genetics 168(3):1763-71
    7) Daniel JA, et al.  (2006) Diverse functions of spindle assembly checkpoint genes in Saccharomyces cerevisiae. Genetics 172(1):53-65
    8) Tong AH, et al.  (2004) Global mapping of the yeast genetic interaction network. Science 303(5659):808-13
    9) Cho RJ, et al.  (1998) A genome-wide transcriptional analysis of the mitotic cell cycle. Mol Cell 2(1):65-73
    10) Iyer VR, et al.  (2001) Genomic binding sites of the yeast cell-cycle transcription factors SBF and MBF. Nature 409(6819):533-8
    11) Spellman PT, et al.  (1998) Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell 9(12):3273-97
    12) Harbison CT, et al.  (2004) Transcriptional regulatory code of a eukaryotic genome. Nature 431(7004):99-104
    13) Bean JM, et al.  (2005) High functional overlap between MluI cell-cycle box binding factor and Swi4/6 cell-cycle box binding factor in the G1/S transcriptional program in Saccharomyces cerevisiae. Genetics 171(1):49-61
    14) Ubersax JA, et al.  (2003) Targets of the cyclin-dependent kinase Cdk1. Nature 425(6960):859-64
    15) Bensen ES, et al.  (2002) A forkhead transcription factor is important for true hyphal as well as yeast morphogenesis in Candida albicans. Eukaryot Cell 1(5):787-98
    16) Horie S, et al.  (1998) The Schizosaccharomyces pombe mei4+ gene encodes a meiosis-specific transcription factor containing a forkhead DNA-binding domain. Mol Cell Biol 18(4):2118-29
    17) Carlsson P and Mahlapuu M  (2002) Forkhead transcription factors: key players in development and metabolism. Dev Biol 250(1):1-23
    18) Badis G, et al.  (2008) A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters. Mol Cell 32(6):878-87