Biology subjects

Kellogg, D. R.

Publications and source records attributed to Kellogg, D. R..

3 recordsLinked to original sources

bioRxiv2023

Hyperactive Ras disrupts cell size control and a key step in cell cycle entry in budding yeast

Severe defects in cell size are a nearly universal feature of cancer cells. However, the underlying causes are unknown. A previous study suggested that a hyperactive mutant of yeast Ras (ras2G19V) that is analogous to the human Ras oncogene causes cell size defects, which could provide clues to how oncogenes influence cell size. However, the mechanisms by which ras2G19V influences cell size are unknown. Here, we found that ras2G19V inhibits a critical step in cell cycle entry, in which an early G1 phase cyclin induces transcription of late G1 phase cyclins. Thus, ras2G19Vdrives overexpression of the early G1 phase cyclin Cln3, yet Cln3 fails to induce normal transcription of late G1 phase cyclins, leading to delayed cell cycle entry and increased cell size. ras2G19V influences transcription of late G1 cyclins via a poorly understood step in which Cln3 inactivates the Whi5 transcriptional repressor. Previous studies found that Ras relays signals via protein kinase A (PKA) in yeast; however, ras2G19Vappears to influence G1 phase cyclin expression via novel PKA-independent signaling mechanisms. Together, the data define new mechanisms by which hyperactive Ras influences cell cycle entry and cell size in yeast. Expression of G1 phase cyclins is also strongly influenced by mammalian Ras via mechanisms that remain unclear. Therefore, further analysis of PKA-independent Ras signaling in yeast could lead to discovery of conserved mechanisms by which Ras family members control expression of G1 phase cyclins.

cell biology↗

bioRxiv2022

The role of an unusual cyclin in control of cell cycle entry and cell size in budding yeast

Entry into the cell cycle in late G1 phase occurs only when sufficient growth has occurred. In budding yeast, a cyclin called Cln3 is thought to link cell cycle entry to cell growth. Cln3 accumulates during growth in early G1 phase and eventually triggers accumulation of late G1 phase cyclins that drive cell cycle entry. All current models for cell cycle entry assume that expression of late G1 phase cyclins is initiated at the transcriptional level. Current models also assume that the sole function of Cln3 in cell cycle entry is to promote transcription of late G1 phase cyclins, and that Cln3 works solely in G1 phase. Here, we show that cell cycle-dependent expression of late G1 phase cyclins does not require cell cycle-dependent transcription. Moreover, Cln3 can influence accumulation of late G1 phase cyclin proteins via post-transcriptional mechanisms. Finally, we show that Cln3 has functions in mitosis that strongly influence cell size. Together, these discoveries reveal surprising new functions for Cln3 that challenge current models for control of cell cycle entry and cell size.

cell biology↗

bioRxiv2020

Analysis of growth-dependent signals that link cell cycle entry to cell growth in budding yeast

Entry into the cell cycle occurs only when sufficient growth has occurred. In budding yeast, the cyclin Cln3 initiates cell cycle entry by inactivating a transcriptional repressor called Whi5. Growth-dependent changes in the concentrations of Cln3 or Whi5 have been proposed to link cell cycle entry to cell growth. However, there are conflicting reports regarding the behavior and roles of Cln3 and Whi5. Here, we found no evidence that changes in the concentration of Whi5 play a major role in controlling cell cycle entry. Rather, the data suggest that cell growth triggers cell cycle entry by driving an increase in the concentration of Cln3. We further found that accumulation of Cln3 is dependent upon homologs of mammalian SGK kinases that play roles in control of cell growth and size. Together, the data are consistent with models in which Cln3 serves as the crucial link between the cell cycle and signals that control cell growth and size.

cell biology↗