CELL CYCLE MODELS: SEQUENTIAL VS PARALLEL PATHWAYS

What are the two conceptual models of cell cycle control?

Sequential model and parallel/alternative pathways model

What does the sequential model propose?

Cell cycle steps occur one after another in a strict order (A→B→C)

What does the parallel model propose?

Multiple processes occur independently and converge later (like factory assembly lines)

Why was the sequential model originally favoured?

Early genetics suggested a single pathway controlled progression

What observation challenged strict sequential thinking?

Many cellular events start before previous ones fully finish

What does a parallel model allow?

Different modules progressing at different times but coordinating at checkpoints

Which organism provided evidence for alternative pathways?

Saccharomyces cerevisiae (budding yeast)

Which CDK features support parallelism?

One CDK (Cdc28) does multiple functions depending on cyclin partner

Why is Cdc28 central to cell cycle function?

It orchestrates budding

Why do cyclins support parallel execution?

Distinct cyclins activate the same CDK for different tasks simultaneously

How do parallel pathways affect timing?

Processes overlap; for example budding begins while DNA replication preparations start

What happens if a cyclin is missing?

Another cyclin may partially compensate

What is a genetic observation supporting parallelism?

cdc31(ts) or cdc7(ts) mutants do not complete division even though cdc28(ts) mutants block everything

What does cdc31(ts) phenotype show?

Some cycle components are interdependent but not all steps depend solely on one gene

What does cdc7(ts) arrest demonstrate?

DNA replication is part of an interlocked module that stalls division even if budding initiates

What happens in cdc28(ts)?

All dependent modules halt — showing Cdc28 sits upstream and integrates multiple inputs

Why do multiple cyclins exist?

To subdivide cell cycle labour into partially independent tasks

How do cyclins make the parallel model work?

Each cyclin drives a module — growth

What indicates process overlap?

Cyclin expression patterns overlap between phases (e.g.

What is the role of checkpoints?

Ensure parallel processes converge correctly before commitment to next stage

What prevents chaos despite parallelism?

CDK thresholds

Why can cells start some tasks before finishing others?

Multiple CDK–cyclin complexes operate at once with different substrate sets

How does START illustrate parallel control?

Budding machinery is activated before replication

Why do separate modules help cell survival?

Redundancy allows flexibility when one pathway is delayed or defective

What is meant by interlocked pathways?

Different branches depend on each other for completion

What supports the notion of interlock?

If cell wall formation or replication fails

What kind of network does the cell cycle represent?

A partially sequential but heavily parallel signalling network

How does parallelism contribute to robustness?

Cells can buffer perturbations and adjust timing without catastrophic failure

Why is strict linearity unlikely biologically?

Cells process thousands of signals and tasks simultaneously

What analogy describes the parallel model?

Factory assembly — multiple parts produced then assembled into a finished product

What triggers convergence of parallel modules?

CDK activity thresholds and checkpoint satisfaction

Why must modules meet before mitosis?

Chromosomes must be replicated

Which phase most clearly illustrates convergence?

G2/M

What does mitotic entry require?

All upstream modules have progressed sufficiently

Why is CDK1 activation switch-like?

Ensures modules are synchronised before irreversible commitment

What happens if one module lags?

Checkpoints delay CDK activation and mitosis

What is a real-world example of module policing?

DNA damage checkpoint pausing Cdc25 and increasing Wee1

Why must checkpoints be strict?

Entry into mitosis with incomplete replication or damage leads to genome instability

Why does the cell not rely on one pathway?

Division requires combined outputs — replication

How does the model explain viability of some mutants?

Cells can re-route or delay events as long as core requirements complete

What does combined defects cause?

Synthetic lethality when more than one module is impaired

Why does the cell cycle feel sequential experimentally?

Many readouts (DNA content

What is the real underlying architecture?

Partially overlapping

Why does understanding the model matter?

Explains checkpoint behaviour