The coordination of cell growth and division by CDK in fission yeast
File(s)
Author(s)
Whyte, Billy
Type
Thesis
Abstract
In the fission yeast, Schizosaccharomyces pombe, mitotic entry is coordinated with the attainment of a particular cell size. This is facilitated by a size homeostasis mechanism that sets the size at division, senses how far the cell is from this set size and promotes or delays mitotic entry accordingly by regulating CDK activity. However, it is unclear how information about size is sensed and integrated into the CDK regulatory network to control mitotic timing.
One way the cell could achieve this is if a molecular correlate of cell size modulated CDK activity in proportion to size. A recent screen of 38 putative G2/M regulators in S. pombe found that only two proteins increase markedly in concentration as cells grow, a behaviour expected of molecules whose abundance encodes cell size: the mitotic B-type cyclin Cdc13 and the Cdc25 phosphatase.
However, cell size at division is relatively robust to changes in the gene dosage of either regulator, consistent with distributive control over mitotic timing. In light of this apparent complexity, efforts were undertaken to define a simplified context in which the regulation coupling CDK activity to cell size is less distributive and more proportionally influenced by the expression of a single gene.
When T-14/Y-15 phosphoregulation of CDK activity is intact, or when other non-essential S-phase cyclins are present, the size control network appears relatively insensitive to changes in Cdc13 abundance. In the absence of both, however, cell size at division becomes much more dependent on the expression level of cdc13.
This could therefore pose a simpler, potentially more tractable, context in which to study cell size control, and raises the question of how these inputs buffer cell size at division against changes in Cdc13 abundance.
One way the cell could achieve this is if a molecular correlate of cell size modulated CDK activity in proportion to size. A recent screen of 38 putative G2/M regulators in S. pombe found that only two proteins increase markedly in concentration as cells grow, a behaviour expected of molecules whose abundance encodes cell size: the mitotic B-type cyclin Cdc13 and the Cdc25 phosphatase.
However, cell size at division is relatively robust to changes in the gene dosage of either regulator, consistent with distributive control over mitotic timing. In light of this apparent complexity, efforts were undertaken to define a simplified context in which the regulation coupling CDK activity to cell size is less distributive and more proportionally influenced by the expression of a single gene.
When T-14/Y-15 phosphoregulation of CDK activity is intact, or when other non-essential S-phase cyclins are present, the size control network appears relatively insensitive to changes in Cdc13 abundance. In the absence of both, however, cell size at division becomes much more dependent on the expression level of cdc13.
This could therefore pose a simpler, potentially more tractable, context in which to study cell size control, and raises the question of how these inputs buffer cell size at division against changes in Cdc13 abundance.
Version
Open Access
Date Issued
2025-09-30
Date Awarded
2026-06-01
Copyright Statement
Attribution-NonCommercial 4.0 International Licence (CC BY-NC)
License URL
Advisor
Nurse, Paul
Sponsor
Francis Crick Institute
Grant Number
PRJ_10908 NURSE WT IA 214183/Z/18/Z
Publisher Department
Institute of Clinical Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)