Cell Cycle Phases and Regulation (2C) - MCAT Biological and Biochemical Foundations of Living Systems

G$1$  S  G$2$  M. The eukaryotic cell cycle progresses sequentially through these phases to coordinate growth, DNA replication, and division, ensuring genetic fidelity.

Cell growth and preparation for DNA synthesis. G$1$ phase enables cellular growth and synthesis of proteins and organelles necessary before committing to DNA replication.

DNA replication (genome duplication). S phase duplicates the genome to provide identical DNA copies for distribution to daughter cells during division.

Growth and preparation for mitosis; DNA damage check. G$2$ phase allows further cellular growth and checks for DNA replication errors to prevent mitotic defects.

Mitosis and cytokinesis to form two daughter cells. M phase divides the nucleus and cytoplasm to produce genetically identical daughter cells.

Quiescent nondividing state entered from G$1$. G$0$ represents a resting state where cells exit the cycle from G$1$ to perform specialized functions without dividing.

G$1$/S checkpoint; commit to division or enter G$0$. The restriction point at G$1$/S evaluates signals to decide on cell division commitment or quiescence.

G$2$/M checkpoint. The G$2$/M checkpoint confirms complete and accurate DNA replication to avoid errors in chromosome segregation.

Spindle assembly checkpoint (metaphase checkpoint). The spindle assembly checkpoint halts mitosis until all chromosomes achieve bipolar spindle attachment for equal segregation.

Serine/threonine kinases that phosphorylate cell-cycle targets. CDKs phosphorylate substrates to regulate transitions between cell cycle phases.

A cyclin. Cyclin binding confers activity and specificity to CDKs for phase-specific phosphorylation events.

Cyclins oscillate; CDK protein levels are relatively constant. Cyclin levels fluctuate to temporally control CDK activity, while CDKs remain stable throughout the cycle.

It inhibits E$2$F and blocks entry into S phase. Hypophosphorylated Rb represses E$2$F to prevent transcription of genes needed for S phase entry.

Rb releases E$2$F, promoting transcription of S-phase genes. Phosphorylation inactivates Rb, allowing E$2$F to drive expression of DNA synthesis genes.

Induces cell-cycle arrest or apoptosis via transcriptional control. p$53$ activates genes for cycle arrest or apoptosis to eliminate damaged cells and maintain genomic stability.

p$21$. p$53$ induces p$21$ to inhibit CDKs, halting progression at G$1$/S in response to damage.

Failure of DNA-damage arrest; increased survival of damaged cells. p$53$ loss impairs damage response, allowing proliferation of mutated cells and promoting tumorigenesis.

Activate checkpoint signaling (for example, via Chk$1$/Chk$2$). ATM/ATR detect damage and phosphorylate effectors like Chk$1$/Chk$2$ to activate checkpoints and arrest the cycle.

E$3$ ubiquitin ligase that triggers anaphase and mitotic exit. APC/C ubiquitinates targets to promote their degradation, enabling anaphase and mitotic progression.

Securin and cyclin B. Ubiquitination of securin activates separase, while cyclin B degradation inactivates CDK$1$ for mitotic exit.

Cleaves cohesin to separate sister chromatids. Separase activation cleaves cohesin rings, enabling sister chromatid separation during anaphase.

Sister chromatid formation (DNA content doubles). DNA replication in S phase forms sister chromatids, doubling DNA without altering chromosome count.

Metaphase of mitosis. Chromosomes condense maximally in metaphase to facilitate alignment and visualization on the mitotic spindle.

Increase cyclin expression to activate CDKs and phosphorylate Rb. Growth factors upregulate cyclins via signaling pathways, activating CDKs to phosphorylate Rb and release E$2$F for S phase genes.