Definitions
- Chromatin: the combination of nucleic acids Nucleic Acids Nucleic acids are polymers of nucleotides, organic molecules composed of a sugar, a phosphate group, and a nitrogenous base. Nucleic acids are responsible for storage, replication, and expression of genetic information. The 2 nucleic acids most commonly seen in eukaryotic cells are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Nucleic Acids and proteins that makes up chromosomes
- Histones:
- Most common protein in chromatin
- Organize DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure, allowing it to be more tightly or loosely wound
- Chromosomes:
- DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure 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 Organelles A cell is a complex unit that performs several complex functions. An organelle is a specialized subunit within a cell that fulfills a specific role or function. Organelles are enclosed within their own lipid bilayers or are unbound by membranes. The Cell: Organelles that function as one 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 one 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 Cytoskeleton A cell's cytosol is the liquid inside the cell membrane that surrounds the organelles and cytoskeleton. The cytosol is a complex solution where many biochemical processes take place. The Cell: Cytosol and Cytoskeleton of a cell along which chromosomes are pulled when they are separated during mitosis
Overview
The cell cycle describes the cyclic sequence of events through which a eukaryotic Eukaryotic Eukaryotes can be single-celled or multicellular organisms and include plants, animals, fungi, and protozoa. Eukaryotic cells contain a well-organized nucleus contained by a membrane, along with other membrane-bound organelles. Cell Types: Eukaryotic versus Prokaryotic, proliferating parent cell splits into 2 identical daughter cells.
G0
- 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.
Interphase
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 RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure 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 DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure 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 Organelles A cell is a complex unit that performs several complex functions. An organelle is a specialized subunit within a cell that fulfills a specific role or function. Organelles are enclosed within their own lipid bilayers or are unbound by membranes. The Cell: Organelles
- Preparation of structures used to move chromosomes ( cytoskeleton Cytoskeleton A cell's cytosol is the liquid inside the cell membrane that surrounds the organelles and cytoskeleton. The cytosol is a complex solution where many biochemical processes take place. The Cell: Cytosol and Cytoskeleton is dismantled)
- Specific proteins that are required for cell division (e.g., RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure molecules) are synthesized.
- Replication is checked using repair mechanisms.
- The cell completes the interphase and is ready for mitosis.
The cell cycle, divided into 5 phases
Image by Lecturio.Cell Division (Mitosis)
During mitosis, the cell’s duplicated DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure is separated and distributed to 2 identical daughter cells. The process lasts approximately 1 hour.
- Prophase:
- 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.
- Prometaphase:
- Kinetochores assemble at the chromosome centromeres.
- Free ends of microtubules connect to the kinetochores.
- Centrosomes reach the opposite poles.
- Metaphase:
- 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.
- Anaphase:
- 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.
- Telophase:
- 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 Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane.
- Both daughter cells are completely separated from each other.
Depiction of stages of mitosis (prophase, prometaphase, metaphase, anaphase, telophase, and cytokinesis): Bottom right corner pictures stained cells in the same phase of mitosis taken by fluorescence microscopy.
Image by Lecturio.Regulation of the Cell Cycle
The cell cycle is tightly regulated. Not passing a checkpoint should trigger programmed cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death (apoptosis). Apoptosis failure results in mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations 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.
- Cyclins:
- 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.
- Cyclins:
- Negative regulators: Activation of these factors blocks the cell cycle.
- p53 and p21: halt cell cycle if DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure damage is detected
- Retinoblastoma Retinoblastoma Retinoblastoma is a rare tumor but the most common primary intraocular malignancy of childhood. It is believed that the condition arises from a neuronal progenitor cell. Retinoblastoma can be heritable or nonheritable. Retinoblastoma protein: halts the G1/S transition
- If hyperphosphorylation occurs due to cyclin-D/CDK 4/6 dimers → transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription of cyclin E and other proteins for progression to S phase begins.
Restriction points
- 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
DNA
The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival.
DNA Types and Structure
- Incomplete genome at this stage will result in cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and 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
DNA
The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival.
DNA Types and Structure damage checkpoints.
- The cell cycle can be arrested until damage has been repaired.
- If the DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure is irreparable, apoptosis is triggered.
Cyclin expression cycle
Image: “Cyclin Expression” by T4taylor. License: Public Domain
Cyclin and cyclin dependent kinases are essential to regulation of the cell cycle. Presence of both proteins is necessary and their activation via phosphorylation permits the progression of the cell cycle.
Image by Lecturio.
1. Protein bound to receptor to activate Ras RAS Renal artery stenosis (RAS) is the narrowing of one or both renal arteries, usually caused by atherosclerotic disease or by fibromuscular dysplasia. If the stenosis is severe enough, the stenosis causes decreased renal blood flow, which activates the renin-angiotensin-aldosterone system (RAAS) and leads to renovascular hypertension (RVH). Renal Artery Stenosis by exchanging guanosine diphosphate (GDP) for guanosine triphosphate (GTP).
Image by Lecturio.
2. Ras RAS Renal artery stenosis (RAS) is the narrowing of one or both renal arteries, usually caused by atherosclerotic disease or by fibromuscular dysplasia. If the stenosis is severe enough, the stenosis causes decreased renal blood flow, which activates the renin-angiotensin-aldosterone system (RAAS) and leads to renovascular hypertension (RVH). Renal Artery Stenosis activates the first kinase (Raf).
3. Raf activates the second kinase (MEK).
4. MEK activates MAP kinases (ERK).
5. MAP kinase (ERK) activates proteins to produce cellular responses, including transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription factors that alter gene expression.
References
- 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.
