# Mitosis
Mitosis
1. Asexual Reproduction
2. Growth & Development
3. Tissue Renewal
## Relevant Proteins & Structures
| Name | Function |
| --------------- | --------------------------------------------------------------------------------------------------------------------------------------------------------- |
| Aurora B Kinase | Checks and regulates microtubule attachment, senses tension via phosphorylation (being pulled away from kinetochores prevents interactions; “tug of war”) |
| | |
| | |
### Centrosomes
- Centrosome creation is just as important as a correct number of DNA replications. If the wrong amount of are present, then an incorrect number of chromosomes could be moved to either side of the cell during division, causing aneuploidy
- **Centrosomes** are composed of *two centrioles* surrounded by the pericentriolar material
- The formation of a new centrosome requires duplication of the centrioles
- Centriole duplication is controlled by the cell cycle and is coordinated with DNA replication
- (IMPORTANT) Centrioles duplicate by the formation and growth of a new centriole immediately adjacent to each existing one
- Do their retain their pair-based relationship (since centrosomes are composed of two)
![[Pasted image 20250115144130.png|300]]
### Kinetochores
### The Spindle
> See also:
> - [[Cytoskeletons]]
The spindle is composed of a mother and a daughter [[Organelles|centrioles]] (in animals)
- Captures the chromosomes and generates the forces for moving the chromosomes and directing where within the cell they will move.
- Very dynamic
![[Pasted image 20250115142857.png|325]]
- Interactions between [[Cytoskeletons|microtubules]] and motors (dynein & kinesin)
## Initiation & Regulation
**Mitosis is orchestrated by several protein kinases**
- The transition from G2 into M phase is a major point of control and is driven by Cdk1 activation
- Several protein kinases are required for proper execution of most mitotic events (most of which are embryonic-lethal or oncogene potentials)
- Polo-like kinases (Plks) can perform regulation in multiple different ways:
- When active, it can phosphorylate Cdc45
- NIMA-like kinases
- Aurora kinases
## The Major Phases
P.M.A.T.
---
Alignment of chromosomes along the metaphase plate relies on an equal amount of tension from both sides that is roughly in the center of the cell
- The chromosomes are pulled
![[Pasted image 20240329211245.png|300]]
### Prophase (Pair)
![[Pasted image 20250115133520.png|325]]
### Metaphase (Middle)
| Protein | Function |
| ------------- | ---------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
| **Cohesin** | Added during S phase to keep sister chromatids together through metaphase. Forms a ring around sister chromatids<br>- aa<br>- Removed at metaphase/anaphase transition |
| **Condensin** | condenses stuff. Added in prophase, removed in telophase |
- Cohesin is added during S phase while condensin is added during prophase
![[Pasted image 20240329213851.png|750]]
At the end of metaphase, cohesin is cleaved
### Anaphase (Apart)
| Protein | Function |
| ------------ | ---------------------------------------------------------------------------------------------------- |
| **Separase** | Cleaves cohesin. It is inhibited by securin, but can be |
| **Securin** | Binds to and *inhibits separase*, preventing it from cleaving cohesin.<br><br>“Keeps things secure.” |
| **CDC20** | Activates the anaphase promoting complex (APC), which leads to degradation of securin and CDKs |
![[Pasted image 20240329211701.png|400]]
**Sister chromatids are held together until anaphase**
- There are several cohesive forces which hold
- Cohesin complex: A “glue” that zips the sister chromatids together
- Separase:
- cleaves cohesin
- is inhibited by securin
- Securin:
- Anaphase promoting complex/cyclosome (APC/C):
- targets securin for destruction
- A type of E3 ubiquitin ligase
#### Chromosome Partitioning
Performed by a collection of motor proteins:
- Eg5 associates with the positive side of the microtubule
- HSET associates with the negative side
- Kinesin
- Dynein
### Telophase (Two)
Cytokinesis