# The Cell Cycle Every time that a [[Cell Division|cell divides]] into two, it goes through a sequence of events collectively referred to as **the cell cycle**. Cells of a multicellular organism will be progressing through the cell cycle *asynhronously*. This means that at any given time, the cells within a sample will be at different stages of the cycle. - One major hurdle in studies of the cell cycle is trying to make these stages as synchronized as possible. ![[Pasted image 20250112172302.png|425]] | Symbol | Phase | Description | | :----: | :-------: | ------------------------------------------------------------------ | | G0 | Gap 0 | | | G1 | Gap 1 | The cell is increasing in size and prepares to replicate it’s DNA. | | S | Synthesis | The cell replicates its DNA. | | G2 | Gap 2 | The cell continues to grow and prepare for cell division. | | M | Mitosis | The cell stops growing and | ## Gap 1 Phase (G1) > [!check] G1 Phase Checkpoint > > During the G1 checkpoint, the cell decides whether it will continue on towards cell division or remain in a rest state (G0). > > ## Synthesis Phase (S) > See also: > - [[DNA Replication]] > - [[DNA Repair and Recombination]] - Once fired, origins of replication can’t be reused until the next cell cycle > [!check] S Phase Checkpoint > > Throughout the S phase, DNA is continuously monitored for replication errors. > > *If DNA synthesis progresses without errors*, growth signals will stimulate the cell to proceed to G2, during which the cell matures. > > ### Verifying DNA Replication > See also: > - Ataxia Telangiectasia Mutated (ATM) ## Gap 2 Phase (G2) ## Mitosis (M) > See also: > - [[Mitosis]] M-Phase Promoting Factor (MPF) ## Cell Cycle Proteins ![[Pasted image 20250115133831.png|475]] ### Cyclins & Cyclin Dependent Kinases (CDKs) A **cyclin-dependent kinase (CDK)** partners with different cyclins during different phases of the cell cycle to phosphorylate distinct sets of target proteins. - Cyclin-dependent kinases (CDKs) are the master regulators of the cell cycle - CDKs are often grouped according to the phase of the cell cycle they correspond to (i.e. CDK) - CDKs partner with different types of *cyclins* during different phases of the cell cycle and proceed to phosphorylate other proteins which drive the cell cycle forward > [!info]- **Cyclin Concentrations During Cell Cycle** > ![[Pasted image 20250122151331.png|650]] **Cyclins** are proteins that oscillate in abundance during the cell cycle. - *Cyclin boxes* are the regions which interact with CDKs, however, this alone barely increases the CDK’s activity - Cyclin levels oscillate as the cell cycle progresses, allowing them to influence the activation levels of CDKs accordingly | Name | Cyclin Partner | Phase Control | Specific Function | | ---- | -------------- | ----------------------- | ------------------------ | | CDK4 | Cyclin D1/2/3 | G1 Phase | | | CDK6 | Cyclin D1/2/3 | G1 Phase | | | CDK2 | Cyclin E | G1 → S Phase Transition | | | CDK2 | Cyclin A | S Phase | | | CDK1 | Cyclin A | G2 → M Phase Transition | | | CDK1 | Cyclin B | Mitosis | M-Phase Promoting Factor | CDK activity can be regulated through various means: - Binding of *cyclin-dependent inhibitor proteins (CKIs, CDIs, or CDKIs)* - Degredation of cyclin - Importing of CDK into the nucleus - Phosphorylation of CDK - Regulated by several means - Subcellular localization - Proteolysis - Inhibitory proteins - phosphorylation - Inhibitors ### CDK Inhibitors (CKIs) https://en.wikipedia.org/wiki/CDK_inhibitor ie p16, p27 ## Regulation of The Cell Cycle > See also: > - [[Biological Signaling]] - Movement through the cell cycle is regulated by *cyclins* and *cyclin-dependent kinases (CDKs)* - Retinoblastoma proteins (RB) will inhibit cellular growth, but can be phosphorylated/blocked by some CDKs - ATM is a powerful protein kinase that is upregulated when DNA damage is detected within a cell. - It will inhibit many checkpoints of the cell cycle and also promote the activation of various DNA repair mechanisms ## Unique Cell Cycle Behaviors ### Embryonic Cell Cycles > See also: > - [[Meiosis]] Embryonic cells often don’t need to go through the G1 and G2 gap phases as they already have an abundance of resources readily available to support the cell during the division process. 1. Gap Phase (G0): A resting cell 2. Growth (G1): Prepare for DNA replication 3. Synthesis (S): Replicate DNA (2n 4. Growth (G2) - Grow in preparation of division/mitosis - Also called interphase 5. Mitosis (M)