The WHI1+ gene of Saccharomyces cerevisiae tethers cell division to cell size and is a cyclin homolog.

Abstract

WHI1‐1 is a dominant mutation that reduces cell volume by allowing cells to commit to division at abnormally small sizes, shortening the G1 phase of the cell cycle. The gene was cloned, and dosage studies indicated that the normal gene activated commitment to division in a dose‐dependent manner, and that the mutant gene had a hyperactive but qualitatively similar function. Mild over‐expression of the mutant gene eliminated G1 phase, apparently entirely relaxing the normal G1 size control, but revealing hitherto cryptic controls. Sequence analysis showed that the hyperactivity of the mutant was caused by the loss of the C‐terminal third of the wild‐type protein. This portion of the protein contained PEST regions, which may be signals for protein degradation. The WHI1 protein had sequence similarity to clam cyclin A, to sea urchin cyclin and to Schizosaccharomyces pombe cdc13, a cyclin homolog. Since cyclins are inducers of mitosis, WHI1 may be a direct regulator of commitment to division. A probable accessory function of the WHI1 activator is to assist recovery from alpha factor arrest; WHI1‐1 mutant cells could not be permanently arrested by pheromone, consistent with a hyperactivation of division.

The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation

“…As protein synthesis seems to increase exponentially during the cell (a) scheme of the start network with components and interactions. Briefly, the Cdk-cyclin complex formed by Cln3 [16][17][18][19][20] and Cdc28 21 phosphorylates the transcriptional repressor Whi5 22,23 and activates sBF (swi6/swi4) and mBF (swi6/mbp1) transcription factors 14 to induce the G1/s regulon 15 and trigger cell cycle entry. Whi3 and Ydj1 act as negative and positive regulators, respectively, of release of cyclin Cln3 from the ER [31][32][33] to allow its accumulation in the nucleus.…”

“…We next analysed the role of Cln3, the most upstream G1 cyclin that activates Start [16][17][18][19][20] . We observed a clear dependence of cell size at Start on growth rate in Cln3-deficient cells (Fig.…”

The role of c-myc in cellular growth control

“…Indeed, the small cell size phenotype found in yeast over-expressing G1 regulators holds true even in complex multicellular tissues (Cross, 1988;Nash et al, 1988;Neufeld et al, 1998). For example, increased numbers of small cells were found in the wing web of Rb-de®cient and E2F-overexpressing Drosophila mutants, clearly demonstrating that growth signals fall upstream of cell cycle controls.…”

Degradation of Ndd1 by APC/CCdh1 generates a feed forward loop that times mitotic protein accumulation

“…Cells were either harvested immediately or washed and released into fresh medium and harvested at the indicated time points. Mitotic cells were obtained by treating exponentially growing cells with 15 mg ml À 1 Nocodozole (Sigma) for 2 h. Cell samples for FACS analysis were collected simultaneously and processed and analysed as described by Nash et al 56 on a FACSAriaIII (BD Biosciences). For budding, index samples were fixed in 12.5% formaldehyde and washed with double-distilled water before counting.…”