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, <9843569 href="#S000059825">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).9843569>
Last updated: 2007-01-25