KA Biology Unit 3 Notes

Unit 3: The Cell Cycle and Differentiation

The Cell Cycle and Mitosis

Wednesday - 2/5/2025

All cells are produced through the process of cell division, during which one cell splits into two. 

Without cell division, you wouldn’t be able to heal after an injury as you can’t grow back blood or skin cells.

Cell division is central to three biological processes: reproduction, organism growth, and cell replacement.

• Reproduction: Cell division is essential for reproduction, or the process by which parent organisms give rise to offspring. In sexual reproduction, two parents produce offspring through the fusion of sex cells, which are the product of cell divisions. In asexual reproduction a single parent produces offspring. This is common in unicellular organisms, where a single cell divides to produce a new, genetically identical organism. In some cases, multicellular organisms can also reproduce asexually through cell division.

• Organism growth: Sexually reproducing, multicellular organisms start life as a single, fertilized egg. This single cell then grows into a mature organism, which can contain anywhere from thousands to trillions of cells! This increase in cell number is the result of repeated cell divisions.

• Cell replacement: When cells are damaged, they are replaced via the division of healthy cells. This process is essential for healing wounds and regenerating tissues. In addition, some tissues require a continuous replacement of cells. For example, bone marrow continuously makes new blood cells to replace those that are naturally degraded or lost due to an injury or bleeding.

Mitosis is a type of cell division that produces genetically identical daughter cells

Mitosis is a form of cell division that produces two cells with identical genetic information. 

These cells are referred to as daughter cells. Prior to mitosis, a cell duplicates its DNA so that it can evenly distribute its genetic material to each daughter cell.

Mitosis involves the splitting of the nucleus, and so only occurs in eukaryotic cells. 

In unicellular eukaryotes, cell division by mitosis results in asexual reproduction. In multicellular eukaryotes, cell division by mitosis is responsible for organism growth, tissue repair, and reproduction.

The accurate division of genetic material relies on chromosome structure

A eukaryotic organism’s genome is split into multiple DNA molecules that are organized into structures called chromosomes, which are found in the nucleus. 

Each chromosome consists of a single, long DNA molecule (that contains many genes) plus supporting proteins.

Together, the DNA and proteins that make up a chromosome are referred to as chromatin. 

Chromatin’s primary role is to tightly package the long strands of DNA into a dense structure that fits inside the nucleus. The basic structural units of chromatin are called nucleosomes, which consist of DNA coiled around proteins called histones.

Prior to mitosis, chromatin is loosely arranged in the nucleus, which means chromosomes cannot be seen individually under a light microscope. 

As a cell gets ready to divide, its chromatin condenses, making its duplicated chromosomes visible under a light microscope. 

Condensed, duplicated chromosomes are often depicted with an “X” shape in diagrams. The condensed form of chromatin ensures that replicated chromosomes are accurately distributed to each of the two daughter cells during mitosis.

When we use the term “mitosis,” we are often referring to the general process of cell division in eukaryotes. 

However, “mitosis” technically describes only one part of the cell division process—the splitting of replicated chromosomes into two nuclei.

In reality, mitosis is just one part of the cell cycle, which is a series of organized and regulated events through which cells grow, replicate their DNA, and ultimately divide. 

This cycle helps cells grow and reproduce properly, ensuring the accurate transmission of genetic material to daughter cells.

Now, what is this cell cycle?

To divide, a cell must complete several important tasks: it must grow, copy its genetic material (DNA), and physically split into two daughter cells. Cells perform these tasks in an organized, regulated series of steps known as the cell cycle.

The cell cycle is split into two primary phases: interphase and the mitotic (M) phase

• During interphase, the cell grows and replicates (makes a copy of) each of its chromosomes. Basically getting ready to divide.

• The mitotic (M) phase is when the cell divides. During the M Phase, the cell separates its chromosomes into two sets and then divides its cytoplasm, forming two genetically identical daughter cells.

Interphase has three subphases

Interphase can be further divided into three subphases known as the G1, S, and G2 phases.

• The G1 phase is when a cell does most of its growing, which requires the cell to take in extra nutrients. During this phase, the cell increases in size, and synthesizes new proteins and organelles.

• The S Phase (synthesis phase) is when a cell replicates its DNA. At the end of this phase, the cell contains a complete copy of each of its chromosomes.

  •  In this stage, chromosomes are not condensed; instead, they are loosely arranged in the nucleus and cannot be seen individually under a light microscope. The cell also continues to grow during this phase.

• During the G2 phase, the cell grows even more and continues to synthesize proteins and organelles. 

• In particular, the cell makes many of the molecules and structures required for the process of cell division, and it also begins to reorganize its contents in preparation for the M Phase

Cells that are ready to divide will complete G2 and enter M phase. However, many cells in the body such as nerve and muscle cells reach a point where their specialized functions are prioritized over cell division, and they no longer divide.

These cells, known as mature cells, exist in the G2 phase and enter a state called G0. G0 is a resting phase of the cell cycle when a cell is not dividing or preparing to divide

Some cells remain here indefinitely, while others may re-enter the process of cell division under the right conditions.

The mitotic (M) phase is only part of the cell cycle. The M phase is divided into mitosis and cytokinesis.

• Mitosis is the division of the cell’s genetic material. 

• Mitosis is broken up into multiple stages, with the later stages overlapping with cytokinesis.

• Cytokinesis is the division of the cell’s cytoplasm.

Mitosis technically describes the splitting of chromosomes into two nuclei, while “cytokinesis” describes the splitting of the cell itself into two new cells.

Mitosis is typically described as happening in stages: prophase, metaphase, anaphase, and telophase. 

These stages are highly regulated and involve detailed coordination of several cell structures. 

One of these structures is the mitotic spindle, which is made up of the same materials as the cytoskeleton, and ensures the equal division of chromosomes between daughter cells.

1. Prophase (sometimes divided into prophase and prometaphase):: Chromatin condenses into chromosomes, nuclear membrane breaks down, spindle fibers form.

1. Chromosomes: In prophase, the chromosomes condense, forming the characteristic “X” shape that is often shown in diagrams. Each “X” is a duplicated chromosome. The two sides of the “X” are called sister chromatids, and they are attached at a point called the centromere. Even though the chromosome has been copied at this point of the cell cycle, as long as the two copies (sister chromatids) are attached, they are considered a single chromosome.

2. Nucleus: The nuclear envelope (the membrane that surrounds the nucleus) breaks into pieces and doesn’t reappear until a later phase (telophase).

3. Mitotic spindle: The mitotic spindle begins to form during prophase, starting at regions called centrosomes. These regions contain the material needed for building the spindle, and also function to regulate the spindle throughout mitosis.

2. Metaphase: Chromosomes line up in the middle of the cell.

1. Chromosomes: In metaphase, the chromosomes are lined up along the metaphase plate (an area in the middle of the cell where chromosomes align). The mitotic spindle is attached to the centromere of each sister chromatid.

2. Mitotic spindle: At this stage, the centrosomes are at opposite ends of the cell and the mitotic spindle is complete. The fibers of the mitotic spindle are elongated. Some fibers overlap at the metaphase plate—these will help push the poles of the cell apart as the cell divides. Other fibers are attached to sister chromatids—these will help pull the sister chromatids apart.

3. Anaphase: Chromatids are pulled to opposite sides of the cell.

1. Chromosomes: In anaphase, sister chromatids separate and begin to move apart. Once separated, each sister chromatid is now considered an individual chromosome.

2. Mitotic spindle: The spindle fibers attached to chromosomes are broken down as the chromosomes move apart. The overlapping spindle fibers push against each other to help the cell elongate.

4. Telophase: Two nuclei form, and chromosomes become less visible.

1. Chromosomes: In telophase, there is now one full set of chromosomes on either side of the cell. At this stage, chromosomes begin to decondense (become loose again).

2. Nucleus: A nuclear envelope begins to assemble around each set of chromosomes.

3. Mitotic spindle: The mitotic spindle completely breaks down.

Cytokinesis: Cytokinesis begins during the late stages of mitosis, typically in anaphase or telophase. 

During cytokinesis, the plasma membrane is drawn inward until the cytoplasm is pinched in two. Now, each new cell contains its own nucleus and organelles.

The cell cycle is essential for tissue growth, repair, and renewal due to its role in regulating cell division. During growth, cells multiply to promote development and increase tissue mass. 

When tissues are damaged, the cell cycle is activated to replace cells that have been lost or injured. For tissue renewal (such as in the skin, blood, or intestinal lining) cells divide to replace old and dying cells, thereby ensuring tissue health. 

Overall, the cell cycle and its regulation of cell division play a crucial role in maintaining healthy tissues in an organism.

Regulation of the Cell Cycle and Cancer

Thursday - 2/6/2025

As cells grow and divide, they go through a series of organized, regulated events called the cell cycle. The cell cycle is split into two primary phases: interphase and the mitotic phase.

• Interphase consists of the G1 (growth), S (DNA synthesis), and G2 (growth) phases. Cells that exit the cell cycle during interphase enter a non-dividing state called G0.

• The mitotic (M) phase consists of mitosis (division of genetic material) and cytokinesis (division of the cytoplasm). During the M phase, the cell divides to form two new daughter cells.

The cell cycle is essential for cell growth and reproduction, as well as the repair of damaged tissues.

The cell cycle is highly regulated

Uncontrolled cell division can be harmful to an organism, so the cell cycle is highly regulated. This regulation is carried out by specific proteins and other molecules, which ensure that the cell only divides when appropriate (such as when enough nutrients are available). A cell’s regulatory factors can be categorized as either internal or external regulators.

• Internal regulators are proteins and other molecules within the cell that help it to divide at the correct rate and under the right conditions. These regulators allow the cell cycle to move forward only after certain events inside the cell have taken place.

• External regulators are signals from outside the cell. These signals help regulate the cell cycle based on environmental conditions and other external factors.

Internal regulators are part of the cell cycle control system—a set of molecules whose abundance and/or activity repeatedly rises and falls in the cell, helping to coordinate key events of the cell cycle, such as the entry into mitosis.

Two important regulators in the cell cycle control system are cyclins and cyclin-dependent kinases (CDKs).

• Cyclins are proteins that are synthesized (made) and broken down at specific times during the cell cycle, which causes their levels to rise and fall at different points in time. When cyclins are present, they bind (attach) to and activate another key internal regulator: the cyclin-dependent kinases (CDKs).

• Cyclin-dependent kinases (CDKs) are  enzymes that interact with specific cellular components related to the cell cycle. CDKs are typically present in the cell but are inactive, requiring the presence of cyclins to become active.

When cyclins bind to CDKs, the shape of the CDKs change, causing them to become active. These active cyclin-CDK  complexes then interact with specific molecules in the cell, leading to events necessary for the cell cycle to move forward.

Maturation-promoting factor (MPF) (also known as M-phase-promoting factor or mitosis-promoting factor) is a cyclin-CDK complex that regulates the transition of a cell from the G2 to the mitotic (M) phase of the cell cycle. MPF is made up of two proteins: cyclin B and CDK1.

• Cyclin B is a cyclin whose levels vary during the cell cycle. Cyclin B levels increase during the S and G2 phases, and peak during the M phase.

• CDK1 is a cyclin-dependent kinase that is always present in the cell, but is only activated when bound to cyclin B.

When cyclin B and CDK1 bind, they become active MPF. So, as cyclin B levels increase, the activity of MPF in the cell also increases. MPF affects downstream targets involved in chromosome condensation, nuclear envelope breakdown, and the formation of the mitotic spindle. When the level of MPF activity is high enough, the cell enters mitosis.

Toward the end of mitosis, cyclin B is broken down, leading to a decrease in MPF activity. As a result, the cell exits mitosis and completes the cell division process. This allows the cell to enter the G1 phase, thus beginning the cell cycle again.

External regulators are signals from outside the cell

External regulators are signals from outside the cell that influence cell division. These signals allow the cell to respond to its environment, and to the needs of the organism as a whole. External regulators can be physical or chemical in nature. Two important physical regulators are known as density-dependent inhibition and anchorage dependence.

• Density-dependent inhibition (or contact inhibition) describes a cell’s response to physical contact with neighboring cells. When cell-surface proteins on two adjacent cells bind, signals are sent to both cells to stop dividing. This ensures that cells are growing at an optimal density in the body.

• Anchorage dependence describes how a cell must be attached to some sort of surface or extracellular matrix in a tissue in order to divide. This ensures that cells are growing in an optimal location in the body.

Important chemical regulators of the cell cycle include hormones and growth factors.

• Hormones are molecules produced by certain glands in the body and released into the bloodstream. Once in the blood, they can travel to and act on distant target cells. Hormones can act to encourage or suppress cell division, depending on the needs of the organism.

• Growth factors are proteins that are released by certain cells into the extracellular environment. These proteins then bind to and stimulate other cells to divide. For example, platelet-derived growth factor (PDGF) is a type of molecule that stimulates cell division to help repair wounds and damaged blood vessels.

Checkpoints of the cell cycle

Cell cycle checkpoints are quality control mechanisms that make sure the cell cycle progresses without errors. At each checkpoint, certain internal and external conditions must be met in order for the cell to move forward with the cell cycle. Cell cycle checkpoints help avoid errors in cell division that could lead to diseases such as cancer.

There are a number of checkpoints, but the three most important ones are the G1, G2, and M checkpoints.

• The G1 checkpoint occurs at the G1/S transition of the cell cycle. At this checkpoint, factors such as cell size, nutrient availability, molecular signals (such as growth factors), and whether the cell’s DNA is damaged determine if the cell moves to the next phase. If conditions are suitable, then the cell progresses from the G1 phase to the S phase. If not, the cell will exit the cell cycle and enter the non-dividing G0 state.

• The G2 checkpoint occurs at the G2/M transition of the cell cycle. A cell will only move past this checkpoint if its DNA was correctly replicated during the S phase. If errors or damage to DNA are detected, the cell will pause at the G2 checkpoint so that the DNA can be repaired. If the damage is irreparable, the cell may self-destruct in a process known as apoptosis, or programmed cell death.

• The M checkpoint (also called the spindle checkpoint) occurs between metaphase and anaphase of mitosis. At this checkpoint, chromosomes must be properly attached to the mitotic spindle at the metaphase plate for the cell to move to the next phase. Only then will the separation of sister chromatids begin. This checkpoint ensures that daughter cells receive the correct number of chromosomes.

An unregulated cell cycle can lead to tumors

The cell cycle is the series of organized events that cells go through as they grow and divide. 

These events are normally tightly regulated by the cell. However, there are times when this regulation breaks down and cells begin to divide uncontrollably. This can result in lumps of tissue in the body called tumors. 

Some tumors are benign (non-cancerous) and do not spread to other parts of the body. Others are malignant (cancerous), and they do spread to other parts of the body.

Cancer is a disease of uncontrolled cell division.

Cancer is a disease in which some of the body’s cells divide uncontrollably, spread to other parts of the body, and invade healthy tissues. In cancer cells, the mechanisms that regulate the cell cycle no longer function properly. Cancer cells develop from normal cells as a result of mutations (changes) in genes involved in cell cycle regulation.

• In normal cells, some genes encode proteins that inhibit (prevent) cell growth and division. In cancer cells, these genes are often mutated so that they no longer inhibit cell division.

• Other genes in normal cells encode proteins that promote (encourage) cell growth and division. In cancer cells, these genes are often mutated so that they are overactive, continually promoting cell division.

Groups of cancer cells typically acquire more and more mutations as they divide.

Oncogenes and tumor-suppressor genes

There are two important classes of genes whose mutations can lead to the development of cancer: tumor suppressor genes and oncogenes.

Tumor-suppressor genes

Tumor-suppressor genes are genes that normally inhibit cell growth and division (called negative cell-cycle regulators). When working correctly, tumor-suppressor genes prevent the formation of cancerous tumors. However, some mutated forms of these genes can no longer function, so they lose their ability to inhibit tumor formation.

Oncogenes

Oncogenes are the mutated forms of genes that normally promote cell growth and division (called positive cell-cycle regulators). Oncogenes are overactive, promoting cell division under conditions when a normal cell would not divide. The normal form of an oncogene without mutations is called a proto-oncogene.

Cancer treatments

Cancer can be a serious disease, but treatments are available. Traditional treatments for cancer include surgery, radiation therapy, and chemotherapy.

• Surgery involves a surgeon physically removing tumors from the body.

• Radiation therapy uses high-energy particles or waves to destroy cancer cells. Radiation damages cancer cells’ DNA enough so that the cells stop dividing and die. The dead cancer cells are broken down and removed by the body.

• Chemotherapy involves drugs that target rapidly dividing cells, aiming to stop the growth and spread of cancer cells. Chemotherapy often affects normal cells as well, leading to side effects such as nausea and hair loss.

Over the years, there have been major advancements in cancer treatment. Newer treatments aim to minimize negative side effects, and are more precise in the types of cancer that they can target. For example, immunotherapy uses the body's own immune system to combat cancer, and targeted therapy employs drugs to precisely target and destroy cancer cells, sparing healthy cells. Additionally, hormone therapy is used to treat certain cancers by blocking or adding hormones to inhibit cancer growth.

Through research, scientists continue to deepen our understanding of cancer and its causes. Each new discovery helps lead to more effective treatments, improving the lives of cancer patients and their families.

Fertilization, Growth, and Cell Differentiation

Friday - 2/7/2025

Reproduction is the process by which parent organisms create new organisms (offspring). When organisms reproduce, they pass their genetic information to their offspring. There are two main forms of reproduction: asexual and sexual reproduction.

• During asexual reproduction, a single parent produces offspring. Each of the offspring has the same genetic information as the parent. This type of reproduction is common among single-celled organisms such as bacteria and protists.

• During sexual reproduction, two parents together produce offspring. The offspring have a mix of genetic information from both parents. This type of reproduction is common among multicellular eukaryotic organisms, which includes humans.

Fertilization is the fusion of gametes

During sexual reproduction, sex cells (known as gametes) from two different individuals (parents) fuse to form a new organism. Each gamete has half of the number of chromosomes compared to a typical body cell. In biological males, gametes are called sperm, and in biological females, gametes are called eggs.

The fusion of gametes (an egg and a sperm) is called fertilization. When the egg and sperm cell fuse, they become a zygote. The zygote now has the full number of chromosomes that the organism needs.

After fertilization, the zygote undergoes many mitotic cell divisions, growing into a mature organism through a process called development.

Haploid and diploid cells

Cells can be classified as haploid or diploid based on the number of chromosome sets they contain. Haploid cells have one complete set of chromosomes, while diploid cells contain two complete sets of chromosomes. The haploid state is designated as "n", and the diploid state is designated as "2n".

Gametes are haploid, while most somatic (body) cells are diploid. The transition between these two states is crucial in reproduction, where haploid gametes merge during fertilization to form a diploid zygote, setting the stage for the development of a new organism.

Human development

Human development begins with fertilization, then progresses through multiple stages as cells divide and change, and organs form. The main stages of human development are the zygotic, embryonic, and fetal stages.

• Zygotic stage: The zygotic stage begins at fertilization with the fusing together of a sperm and an egg. The single-celled zygote contains all of the genetic material needed to develop into a mature human.

• Embryonic stage: As soon as the zygote divides, it becomes an embryo. Early in embryonic development, the embryo is a blastocyst—a hollow ball of cells with an inner cell cluster. During later stages of embryonic development, the basic outline of the body forms, and the heart, brain, and spinal cord become visible.

• Fetal stage: At about eight weeks into pregnancy, all of the major structures of a human are present in rudimentary form, and the embryo becomes a fetus. As the fetus continues to develop, the body’s structures are refined, and the fetus grows in size.

Development involves cell differentiation and morphogenesis

How does a single cell (the zygote) develop into a mature organism with multiple cell types and complex structures? This occurs as a result of two critical processes: cell differentiation and morphogenesis.

Cell differentiation

Cell differentiation is the process by which unspecialized cells are transformed into specialized cells. Specialized cells are those with specific structures and functions, such as nerve cells, muscle cells, and blood cells.

The zygote and the cells of the early embryo can give rise to the specialized cells of the mature organism because they are stem cells. Stem cells have the ability to divide many times while remaining unspecialized, and also to differentiate into specific cell types. Stem cells differ in the number of cell types they can become.

• The zygote is a totipotent stem cell, which means it can give rise to any kind of human cell. This includes the cells that make up the embryo, and also the cells that make up tissues that support the embryo during pregnancy, such as those of the placenta.

• The blastocyst’s inner cell cluster is pluripotent, which means the cells can give rise to any type of cell in the embryo.

Morphogenesis

Following cellular differentiation, the embryo undergoes morphogenesis, which is the process that shapes the physical form of the developing organism.

During morphogenesis, specialized cells move around and rearrange themselves, organizing into complex structures and tissues. For example, after the embryo implants into the wall of the uterus, gastrulation occurs. During this process, cells move to form three layers, each of which turns into specific parts of the body: the ectoderm becomes the skin and nervous system, the mesoderm becomes the muscles and bones, and the endoderm becomes internal organs, such as the lungs and liver.

How is cell fate determined during cell differentiation and morphogenesis?

The cells in a mature multicellular organism are derived from a single cell (the zygote), so each cell contains the same genetic information. In other words, liver cells, muscle cells, epithelial cells, and almost every other type of cell in the body contain the same chromosomes, and therefore the same genes.

How, then, can specialized cells have such unique structures and functions? Cells specialize by using only a subset of their genes during and after differentiation. In other words, only certain genes are expressed, or used to make proteins, in a given cell type.

The different patterns of gene expression that lead to specialized cells begin early in the embryo’s development. There are two primary mechanisms by which these gene expression patterns are established: cytoplasmic determinants and inductive signals.

• Cytoplasmic determinants are substances found in the cytoplasm that influence gene expression patterns. These substances, which include specific RNA and protein molecules, are unevenly distributed within the cytoplasm of an egg cell. This means that when a zygote undergoes its first few divisions, the resulting cells have different groups of substances in their cytoplasms. As a result, each nucleus is exposed to different cytoplasmic determinants, and therefore initiates different patterns of gene expression.

• Inductive Signals are messages sent between neighboring cells that influence how each cell behaves and develops. For example, when a cell touches or is very close to another cell, it can receive signals through contact with molecules on the surface of the neighboring cell or through growth factors released by the cell. These signals can trigger changes in the receiving cell’s gene expression, leading it to follow a specific developmental pathway. As a result, the cell begins to produce proteins that are specific to a certain type of tissue, helping to form the body’s different tissue types.