- Chromatin: the combination of nucleic acids and proteins that makes up chromosomes
- Most common protein in chromatin
- Organize DNA, allowing it to be more tightly or loosely wound
- DNA and protein-containing subunits in which genes are organized
- Usually string-like and diffuse, during mitosis condense into discrete rod-like structures
- Sister chromatid: 1 of 2 identical halves of a replicated chromosome
- Centrioles: cylindrical organelles that function as 1 of the attachment poles of the mitotic spindle in a replicating cell (the other end being a kinetochore)
- Centrosomes: organelle containing centrioles
- Kinetochore: protein structure that attaches to the central zone of a chromosome (centromere) to which 1 of the ends of the mitotic spindle attaches in a replicating cell (the other end being the centrioles)
- Centromeres: the region of the chromosome to which the microtubules of the mitotic spindle attach via the kinetochore
- Mitotic spindle: the microtubule structure created from the disassembled cytoskeleton of a cell along which chromosomes are pulled when they are separated during mitosis
The cell cycle describes the cyclic sequence of events through which a eukaryotic, proliferating parent cell splits into 2 identical daughter cells.
- Mature, differentiated cells outside the cell cycle are in this reversible, resting state.
- Low concentration of growth factor and high population density keep cells in G0.
- Normal metabolism occurs, but there is no cell division.
- Specific triggers, such as growth factors, induce some cells to return to G1.
G1, S, and G2 phases are grouped together as interphase.
- G1 (gap 1): duration = approximately 12 hours
- Occurs immediately after mitosis (cell is half its normal size)
- Period of cell-volume growth
- RNA and protein synthesis take place.
- Proteins and cellular constituents required for mitosis (e.g., microtubules) are created.
- S (synthesis): duration = 8–12 hours
- Chromosomes double, creating identical pairs of sister chromatids (diploid → tetraploid set)
- Quality assurance phase:
- Ensures the accuracy of replication
- DNA mismatch repair occurs
- Machinery for mitosis is prepared:
- Centrosomes duplicate
- Centriole separate
- Histones synthesized
- G2 (gap 2): duration = 1.5–3 hours
- Replication of certain organelles
- Preparation of structures used to move chromosomes (cytoskeleton is dismantled)
- Specific proteins that are required for cell division (e.g., RNA molecules) are synthesized.
- Replication is checked using repair mechanisms.
- The cell completes the interphase and is ready for mitosis.
Cell Division (Mitosis)
During mitosis, the cell’s duplicated DNA is separated and distributed to 2 identical daughter cells. The process lasts approximately 1 hour.
- Chromosomes condense, becoming visible.
- Microtubules assemble, creating the mitotic spindle attached to the centrioles.
- Centrosomes migrate toward opposite poles of the cell.
- Nucleolus is no longer visible.
- Nuclear envelope begins to dissolve.
- Kinetochores assemble at the chromosome centromeres.
- Free ends of microtubules connect to the kinetochores.
- Centrosomes reach the opposite poles.
- Chromosomes are aligned along the equatorial region (metaphase plate) of the cell.
- Each sister chromatid is attached to a mitotic spindle originating from opposite poles.
- The nuclear envelope completely dissolves.
- Kinetochores break down.
- Sister chromatids become single chromatids or chromosomes.
- Chromatids migrate to opposite poles along the mitotic spindle.
- Spindle fibers opposite the chromatids elongate, stretching the cell into an oval.
- New nuclear envelopes form around the decondensing chromosomes.
- The spindle apparatus dissolves.
- “Cleavage furrow” splits the cell in 2 (cytokinesis)
- Each of the daughter cells develops a complete cell membrane.
- Both daughter cells are completely separated from each other.
Regulation of the Cell Cycle
The cell cycle is tightly regulated. Not passing a checkpoint should trigger programmed cell death (apoptosis). Apoptosis failure results in mutation accumulation, leading to disease.
The cell cycle begins when the cell has:
- A sufficient minimum size
- Appropriate nutritional conditions
- Been stimulated by growth factors, in addition to the absence of anti-mitogenic signals
Molecules regulating the cell cycle
- Positive regulators: Presence at appropriate concentrations permits the cell cycle to progress.
- Regulatory proteins released in response to internal and external stimuli at specific stages of the cell cycle.
- 4 different cyclin concentrations fluctuate predictably during the cycle.
- Cyclin-dependent kinases (CDK) are protein kinases that are:
- Activated by cyclins and protein kinases (via phosphorylation)
- Inhibited by protein phosphatases (via dephosphorylation) and cyclin-dependent kinase inhibitors (CKIs)
- Nuclear localization sequence (NLS) allows cyclins to enter the cell nucleus as a heterodimer with CDKs.
- Negative regulators: Activation of these factors blocks the cell cycle.
- p53 and p21: halt cell cycle if DNA damage is detected
- Retinoblastoma protein: halts the G1/S transition
- If hyperphosphorylation occurs due to cyclin-D/CDK 4/6 dimers → transcription of cyclin E and other proteins for progression to S phase begins.
- Later G1 phase (G1S checkpoint): irreversible
- Regulated by CDK2 and cyclin E
- Transition between the G1 and S phases determines cell progression to cell division or dormancy in G0 phase.
- End of the G2 phase (G2M checkpoint)
- Regulated by CDK1 and cyclin B
- Checkpoint for favorable environmental conditions and correct and complete replication of DNA
- Incomplete genome at this stage will result in cell death.
- M-phase promoting factors (MPF), which are cyclin-CDK heterodimers, play an important role in this checkpoint.
- During metaphase (spindle checkpoint): irreversible
- Ensures that all chromosomes adhere to the spindle microtubules prior to separation in anaphase
- Tension on the spindle fibers → production of anaphase-promoting complex (APC)
- APCs promote breakdown of connexin (kinetochore) proteins between sister chromatids.
- G1 and G2 phases have further DNA damage checkpoints.
- The cell cycle can be arrested until damage has been repaired.
- If the DNA is irreparable, apoptosis is triggered.
- Clark, M. A. et al. (2018). Biology 2e. https://openstax.org/details/books/biology-2e?Book%20details
- Goljan, E. F. (2013). Rapid review pathology: with student consult online access. Elsevier Health Sciences.