The Cell Cycle

Overview of the Cell Cycle

  1. S (synthesis) phase: cell replicates its DNA

  2. M phase: nucleus divides in a process called mitosis, then the cytoplasm divides in a process called cytokinesis

  3. G1: gap between M phase and S phase

  4. G2: gap between S phase and M phase

The cell cycle control system ensures that…

  • the environment is favorable for the cell to initiate DNA replication

  • All chromosome are attached to mitosis spindle before the chromosomes are segregated to the two daughter cells

  • All DNA is replicates before M phase begins

  • The M phase does not have to be completed before cytokinesis begins, as cytokinesis is a part of the M phase


The Cell-Cycle Control System

Cyclin-dependent kinases (Cdk) are always present in the cell, but they are only active when bound to cycling

  • Cyclin levels fluctuate during cell cycle

  • When cycling bind to Cdk, they active the kinase activity complex

  • The kinase activity of the Cdk subunit increases at different stages of the cycle

  • Cdk concentration remains relatively constant

  • Cdk are not degraded → it’s the cycling that are synthesizes and degrades in a regulated manner

Chromosome segregation takes place only after the duplicated chromosomes are corrected aligned to kinetochore proteins that interact with with the microtubules of the mitotic spindle

G1 Phase

  • Cells that divide once per month or once per year spend the vast majority of that time in G0 and G1

  • Most of the diversity rates of cell division in the adult body is due to variation in the length of G1 phase and G0 phase

S Phase

  • S-Cdk activates proteins involved in the initiation of DNA replication

  • DNA replication only occurs during the S phase of the cell cycle

  • S-Cdk activity also helps to prevent re-replication by phosphorylation and inactivates proteins that are needed to form new replication origins

M Phase

  • When phosphorylated, Cdc25 becomes activates, which in turn removes the inhibitory phosphates from M-Cdk, thereby activating more M-Cdk

  • This is an example of a positive feedback loop


Mitosis

Prior to M phase, cell increases in side, DNA of chromosomes is replicates, and centrosome is duplicates

  1. Prophase → the duplicated chromosomes (two closely associated sister chromatids) condense; outside the nucleus, mitotic spindle assembles between two centrosomes, which have begun to move apart

  2. Prometaphase → breakdown of nuclear envelope; chromosomes can attach to spindle microtubules via kinetochores and undergo active movement

  3. Metaphase → chromosomes aligned at equator of the spindle, midway between spindle poles; kinetochore microtubules on each sister chromatid attach to opposite poles of spindle

  4. Anaphase → sister chromatids synchronously separate and are pulled slowly toward spindle poles to which they are attached; kinetochore microtubules get shorter, and spindle poles also move apart, both contributing to chromosome segregation

  5. Telophase → two sets of chromosomes arrive at poles of the spindle; new nuclear envelope reassembles around each set, completing formation of two nuclei and marking end of mitosis; division of cytoplasm begins the assembly of contractile ring

  6. Cytokinesis → cytoplasm divided in two by contractile ring of actin and myosin filaments, which pinches the cell into two daughters, each with one nucleus

The anaphase-promoting complex/cyclosome (APC/C) is a crucial regulator. It’s an E3 ubiquitin ligase that marks specific proteins for degradation, leading to key transitions in the cell cycle

  • APC/C activates separase by targeting securin (an inhibitory protein) for destruction

  • Once securin is degraded, separase becomes actives and cleaves the cohesin proteins that are holding the sister chromatids together

  • This allows the sister chromatids to separate, marking the onset of anaphase


Cytokinesis

The final step of the cell cycle where the cytoplasm of a single parent cell is divided into two daughter cells, ensuring that each daughter cell receives its own nucleus and share of organelles and cytoplasmic contents

In animal cells:

  • contractile ring made of actin and myosin filaments form beneath plasma membrane at cell’s equator

  • Ring contracts, forming a cleavage furrow that pinches the cells in two

In plant cells:

  • cell plate forms in the middle of the cell, built from vesicles containing cell wall materials

  • Plate expands outward until it fuses with plasma membrane, dividing the cell


Control of Cell Growth, Cell Division, and Cell Survival

Mitogens - Stimulate cell division

Mitogens promote the cell cycle, particularly the transition from G1 to S phase by lifting intracellular brakes on proliferation

  • bind to receptors on cell surface and activate signaling pathways

  • Stimulate production of cyclins and activate cyclin-dependent kinases (Cdks)

  • Inhibit proteins (e.g. Rb) that suppress cell cycle progression

  • Example: Platelet-derived growth factor (PDGF)


Growth factors - stimulate cell growth (increase in size and mass)

Growth factors increase protein synthesis and inhibit protein degradation, leading to cell growth (but not necessarily division)

  • Activate PI3K-Akt-mTOR signaling pathways

  • Promote ribosome biogenesis and nutrient uptake

  • Enhance metabolic activity

  • Example: insulin-like growth factor (IGF)


Survival factors - promote cell survival and suppress apoptosis

These signals prevent programs cell death (apoptosis), helping cells survive in their environment

  • activate signaling pathways (like Akt) that inhibit pro-apoptosis proteins (e.g., Bad)

  • Maintain mitochondrial integrity to prevent cytochrome c release

  • Example: nerve growth factor (NGF)