Key result
The cln3 whi5 double mutant yeast cells had a mean size of 56.6 fL, nearly wild-type size (49.7 fL), demonstrating that CLN3 can work independently of WHI5 in regulating cell size.
Why the study?
Previous studies suggested CLN3 and WHI5 regulate cell size at Start in a linear, dependent pathway, motivating investigation of whether CLN3 can act independently of WHI5.
Absolute Event Rate: 56.6% vs 49.7%
p-value: p=9e-32
In yeast, CLN3 can regulate cell size independently of WHI5, challenging the previous model of a strictly linear dependent pathway.
Should not yet change practice; challenges the linear CLN3–WHI5 Start model and leaves mammalian conservation open.
In yeast, cells commit to division at “Start” in G1 phase. The critical cell size for Start is regulated in part by the size-control genes CLN3 and WHI5 . Cln3 is a G1 cyclin that activates Start by activating the Cdc28 cyclin dependent kinase. Null cln3 mutants have large cells, because they lack an activator, while hyperactive mutants have small cells. Whi5 inhibits Start. Null whi5 mutants have small cells, while hyperactive mutants have large cells. Previous studies suggested that CLN3 and WHI5 are in a linear, dependent pathway, in which Cln3 acts inhibits Whi5, possibly by phosphorylation. We compared isogenic WT, cln3, whi5 , and cln3 whi5 mutants, and find that whi5 is not epistatic, or not fully epistatic, to CLN3 —that is, CLN3 can work independently of WHI5 . The cln3 and whi5 deletions have off-setting phenotypes, such that the double mutant is nearly wild-type in cell size, and has only the mildest phenotype, with well-controlled cell size, despite entirely lacking two major cell size regulators. Growth rates were also measured. Some mutants were larger and some mutants smaller than wild-type, but the wild-type had the fastest doubling time, consistent with the idea that wild-type size is optimal for growth rate.
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Honey et al. (2025) studied Yeast cell size control. cln3 and whi5 gene deletions vs. Wild-type (CLN3 WHI5) was evaluated on Mean cell size (fL) (p=9e-32). The cln3 whi5 double mutant yeast cells had a mean size of 56.6 fL, nearly wild-type size (49.7 fL), demonstrating that CLN3 can work independently of WHI5 in regulating cell size.
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