Spontaneous reversion of tsBN67 cell proliferation and cytokinesis defects in the absence of HCF-1 function.
Mammalian HCF-1 is a highly conserved and abundant chromatin-bound protein that plays a role in both herpes simplex virus (HSV) immediate-early (IE) gene transcription and cell proliferation. Its role in cell proliferation has been evidenced through the analysis of a temperature-sensitive hamster cell line called tsBN67. When placed at nonpermissive temperature, tsBN67 cells undergo a stable and reversible proliferation arrest after a lag of 36-48 h. This phenotype results from a single point mutation in HCF-1, which disrupts HCF-1 association with both chromatin and the HSV IE transactivator VP16 at nonpermissive temperature. Here, we report the isolation and characterization of spontaneous tsBN67 growth-revertant cells that are able to proliferate at nonpermissive temperatures. These cells retain the tsBN67 HCF-1 point mutation and grow in the absence of HCF-1 chromatin association, demonstrating that complete restoration of tsBN67 HCF-1 functions is not essential for cell proliferation. Phenotypic analysis of both mutant and revertant tsBN67 cells shows that, in addition to a cell proliferation defect, these cells display a conspicuous multinucleated phenotype in a significant population of arrested cells. This defect in cytokinesis is also a result of loss of HCF-1 function, suggesting that HCF-1 plays a role in cell exit from mitosis. The revertant tsBN67 cells display a coincident restoration of cell proliferation and suppression of the cytokinetic defect, suggesting that HCF-1 plays a shared role in cell proliferation and cytokinesis.
Reilly
Patrick T
PT
Cold Spring Harbor Laboratory, New York 11724, USA.
Herr
Winship
W
D000818:Animals; D015415:Biomarkers; D002455:Cell Division; D002460:Cell Line; D006224:Cricetinae; D016195:G2 Phase; D051863:Host Cell Factor C1; D008938:Mitosis; D010641:Phenotype; D017354:Point Mutation; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D013696:Temperature; D014157:Transcription Factors
D015415:Biomarkers; D051863:Host Cell Factor C1; D011506:Proteins; D014157:Transcription Factors