Cycle Cell Regulation Cheat Sheet:
Ok, heres the warning. This might not be all you need to know about cell cycle control, but I feel like its a great place to start. It should provide you 90+% of what you need. Just make sure that you study your notes in addition to this cheat-sheet. I really feel that some of these concepts need pictures to accompany them, but I will try to explain things as best as possible using words. Please refer to your notes, or find somebody who attends my sections theyve got all the pictures for these words: Cells start in the Gap1 (G1) phase where they grow and finally decide to start the process of division. They enter Synthesis (S) phase, where the cell replicates its genome. The cell then enters the Gap2 (G2) phase where it makes sure that the replication has occurred correctly and it gets ready to undergo cell division. Finally, these cells enter mitosis (M) phase. Each of these steps contains many checkpoints, and the procession of cells through these phases is highly complex and intricately coordinated. You only need to concern yourself with how a cell enters M phase (a late G2 event), and how the cell progresses through M phase. This is described in greater detail below: Gap2: Entry into Mitosis: During G2, Cyclin B is constantly being synthesized, and its levels are slowly rising throughout the cell. When they encounter Cyclin-Dependent Kinase 1 (Cdk1), it will bind to it and form a complex that is sometimes referred to as Mitosis Promoting Factor (MPF). However, it is still too early to enter M phase, so this Cdk1-Cyclin B complex is phosphorylated by two different kinases: CAK (activating phosphate), and Wee1 (master inhibitor phosphate). In this confirmation, it is turned off, but it poised. This poised confirmation builds up over the course of G2. Eventually (through a mechanism not discussed) the phosphatase Cdc25 cleaves off the inhibitory phosphate, leading to the activation of the Cdk1-Cyclin B complex. This complex can then stimulate activity of Cdc25 (leading of more conversion of poised MPF to active MPF), and inhibits the activity of Wee1 (which prevents active MPF being deactivated). Once the Cdk1-Cyclin B complex is switched on, M phase has begun. Prophase: This phase is primarily marked by a condensation of the chromosomes. However, the Cdk1Cyclin B complex is also beginning to find its targets and phosphorylate them. One of these targets is Lamina, the intermediate filament that gives the nucleus its shape. Phosphorylation of Lamina helps lead to a breakdown of the nuclear envelope. Prometaphase: Once the nuclear envelope has broken down, the Mitotic spindle can start forming. To aid in the search and capture of kinetochores, the rate of catastrophe for Microtubules (MTs) is increased. This is due to a disruption in the balance of MT stabilizers and destabilizers (kinesin-13 is a destabilizer, and XMAP215 is a stabilizer that is deactivated during M phase). Once a MT binds a to kinetochore, the + end of that MT is stabilized. The spindle contains three different types of MTs: Kinetochore MT (those bound to the kinetochore), Polar MT (those that overlap with MTs from the other pole), and Astral MT (all the rest, that stick out in crazy directions). Remember that the spindle can form in the absence of
centrosomes because of the presence of Ran-GEF on the chromosomes. This enzyme creates a gradient of Ran-GTP around the chromosomes, which allows for nuclear transport to occur even in the absence of a nucleus and a nuclear pore (so NLS cargos get dropped off near chromosomes). Some of these cargos are MT nucleating factors that will allow for new MTs to form near the chromosomes. Kinesins can then move the MT, so that the + ends are in the middle, and the ends are on the outside. Dynein motors then bundle up the ends into a pole. Spindle Assembly Checkpoint: Mad 1 binds to kinetochores, but is displaced when a MT finally finds and binds to that kinetochore. While Mad1 is bound, it can bind to Mad2, change it (into Mad2* a notation that I have made up for ease of writing). Mad2* can then diffuse throughout the cytoplasm. It recruits Cdc20, and sequesters it, preventing Cdc20 from being incorporated into the Anaphase Promoting Complex (APC/C), meaning that anaphase is delayed until each and every kinetochore is bound by MTs and no Mad1 is bound to kintochores. Metaphase: The point at which all the chromosomes are lined up on the metaphase plate. Anaphase A+B: Anaphase cannot start until the APC/C is activated. APC/C is activated by the Cdk1-Cyclin B complex, but it requires Cdc20 as well. Cdc20 is only released after the Spindle Assembly Checkpoint is passed. Once this occurs, then the APC/C is active. Unlike the other regulatory complexes, APC/C is an E3 ubiquitin ligase, meaning that it poly-ubiquitinates proteins leading to their degredation by the Proteasome. The APC/C targets Securin, degrading it and causing it to release Separase, a protease that cleaves Kleisin, the clasp that is part of the Cohesin ring complex. Cutting Kleisin causes Cohesin to fall off the chromosomes, allowing the sister chromatids to be pulled to their appropriate poles. This is Anaphase A. Anaphase B is where the poles push away from each other. Telophase: In order for the nuclear envelope to enclose each genome, the Cdk1-Cyclin B complex must be shut off. This is accomplished by switching out the Cdc20 subunit of the APC/C for Cdh1, which causes the APC/C to recognize different targets, including Cyclin B. This degradation of cyclin B allows for the reversion of the changes the cell went through in early M phase. This allows the laminar sheet to reform, allowing for the reassembly of the nuclear envelope. Once this occurs, the chromosomes can de-condense. Cytokinesis: Once the nuclear envelopes have reassembled, the two cells pinch off from each other by the use of a contractile ring made of Actin and Myosins.