Stochasticity and homeostasis in the E. coli replication and division cycle

Area of Science:

• Cell Biology
• Microbiology
• Systems Biology

Background:

• Cellular processes like chromosome replication and division exhibit inherent variability (stochasticity).
• Understanding how cells manage this variability to maintain coordinated cell cycles is crucial but poorly understood.
• The precise timing and control mechanisms linking DNA replication to cell division remain an active area of research.

Purpose of the Study:

• To investigate how cells compensate for stochasticity in cell size and growth rate during the cell cycle.
• To determine the roles of different cell cycle phases (B, C, and D periods) in coordinating chromosome replication and cell division.
• To test the hypothesis that replication initiation is the primary trigger for cell division.

Main Methods:

• Utilizing time-lapse microscopy to observe cell behavior over time.
• Employing fluorescently labeled SeqA protein to track key cell cycle events: birth, DNA replication initiation, replication termination, and cell division.
• Measuring cell size and growth rates throughout the cell cycle.
• Applying an auto-regressive theoretical framework to model and compare different control mechanisms.

Main Results:

• The time from cell birth to DNA replication initiation (B-period) compensates for variations in initial cell size and growth rate.
• The time from replication termination to cell division (D-period) also compensates for cell size and growth rate variability.
• The duration of DNA replication (C-period) did not show compensatory behavior for size and growth variability.
• A slight, systematic shortening of the C-period was observed in faster-growing cells, suggesting a link between metabolism and replication timing.

Conclusions:

• Cell cycle timing relies on compensatory mechanisms within the B and D periods to buffer against stochasticity.
• Replication initiation is not the sole or principal trigger for cell division; the D-period plays a significant role.
• Metabolic fluctuations may influence DNA replication timing, indicating a potential coupling between cellular metabolism and genome duplication.