Cell Cycle Definition
The cell cycle is a series of events that occur in a cell as it grows and divides into two daughter cells. It consists of four stages: Gap 1 (G1), Synthesis (S), Gap 2 (G2), and Mitosis. During the G1 stage, the cell grows and prepares for DNA replication. In the S stage, DNA replication occurs. In the G2 stage, the cell continues to grow and prepares for mitosis. Finally, during mitosis, the cell divides into two daughter cells.
What is the Cell Cycle?
The cell cycle is a series of events that occur in a cell as it grows and divides into two daughter cells. The cell spends most of its time in interphase, which is divided into three stages: G1, S, and G2. During the G1 stage, the cell prepares to divide.
In the S stage, the cell copies all its DNA. After the DNA is copied and there is a complete extra set of all genetic material, the cell moves into the G2 stage where it organizes and condenses genetic material.
The M phase consists of mitosis and cytokinesis. During mitosis, the parent cell goes through a complex series of steps to ensure that each daughter cell will get the materials it needs to survive, including a copy of each chromosome. Cytokinesis separates all components of the parent cell into two daughter cells.
The eukaryotic cell cycle consists of four distinct phases: G1 phase, S phase (synthesis), G2 phase (collectively known as interphase), and M phase (mitosis and cytokinesis). The stages G1, S, and G2 make up interphase which accounts for the span between cell divisions.
Cells use special proteins and checkpoint signaling systems to ensure that the cell cycle progresses properly. Checkpoints at the end of G1 and at the beginning of G2 are designed to assess DNA for damage before and after the S phase.
Likewise, a checkpoint during mitosis ensures that spindle fibers are properly aligned in metaphase before chromosomes are separated in anaphase.
The function of the Cell Cycle
The cell cycle is a series of events that takes place in a cell as it grows and divides. The most basic function of the cell cycle is to duplicate accurately the vast amount of DNA in the chromosomes and then segregate the copies precisely into two genetically identical daughter cells.
The cell cycle has different stages called G1, S, G2, and M. During interphase (G1, S, and G2), the cell grows, replicates its chromosomes, and prepares for cell division. In the S phase, the cell copies all its DNA.
The M phase is when mitosis occurs – this is where the duplicated chromosomes are separated into two nuclei. Mitosis consists of four phases: prophase, metaphase, anaphase, and telophase.
During prophase, centrosomes separate and migrate to opposite poles; chromatin transforms into chromosomes composed of pairs of filaments called chromatids; and the nuclear membrane disappears.
In metaphase, paired chromosomes become lined up between the centrioles. In anaphase, chromatids are pulled toward opposite poles by spindle fibers. Finally, during telophase, new nuclear membranes form around each set of separated chromatids.
The accurate duplication of DNA during interphase followed by precise segregation during mitosis ensures that each daughter cell receives a full copy of genetic material without any errors or unequal division. Mistakes during copying or unequal division can lead to unhealthy or dysfunctional cells that may cause diseases.
Phases of Cell Cycle
The cell cycle consists of four stages: Gap 1 (G1), Synthesis (S), Gap 2 (G2), and Mitosis
G1 Phase
The cell cycle is composed of interphase (G1, S, and G2 phases), followed by the mitotic phase (mitosis and cytokinesis), and the G0 phase. The G1 phase is the first gap phase where the cell grows physically larger, copies organelles, and makes molecular building blocks it will need in later steps.
Proteins and RNAs are synthesized during this phase, along with centromeres and other components of centrosomes. In the S phase, the cell synthesizes a complete copy of the DNA in its nucleus. It also duplicates a microtubule-organizing structure called the centrosome.
The centrosomes help separate DNA during the M phase. Finally, the G2 phase involves further cell growth and organization of cellular contents.
The G1 checkpoint is one of three checkpoints in the cell cycle. Before entering G1, cells go through the Exit M checkpoint to ensure that they have completed mitosis and are ready for the first growth phase. Once this transition phase is passed, cells are ready for the G2 phase.
S Phase
The S phase is a stage in the eukaryotic cell cycle during which DNA replication occurs. The cell cycle of most eukaryotic cells is divided into four phases: M, G1, S, and G2. M phase (mitosis) is usually followed by cytokinesis. During the S phase, the cell copies all of its DNA in preparation for cell division.
Variations of cell labeling experiments can be used to determine the length of different stages of the cell cycle. For example, an experiment in which cells are exposed to radioactive thymidine for 15 minutes can determine the fraction of cells in the S phase.
DNA damage can arrest the cell cycle in G2 and slow progression through the S phase. This allows time for repair before damaged DNA is replicated during the S phase.
G2 Phase
The G2 phase is the third and shortest phase of interphase in the cell cycle. During this phase, the cell prepares itself for mitosis by producing organelles and proteins necessary for cell division.
The cell grows physically larger, copies organelles, and makes molecular building blocks it will need in later steps during the first gap phase (G1). In the S phase, the cell synthesizes a complete copy of DNA in its nucleus and duplicates a microtubule-organizing structure called the centrosome.
The G2 phase is not a necessary part of the cell cycle as some cells proceed directly from DNA replication to mitosis. However, most cells go through G2 before entering mitosis.
Mitotic entry is determined by a threshold level of active cyclin-B1/CDK1 complex or maturation-promoting factor (MPF). Active cyclin-B1/CDK1 triggers irreversible actions in early mitosis including centrosome separation, nuclear envelope breakdown, and spindle formation.
During the G2 phase, cells synthesize mitotic components and segregate duplicated DNA into equivalent or nearly equivalent daughter cells. Cells respond to DNA damage or incomplete replication by arresting at the G2/M checkpoint until a repair is completed.
Mitosis
Mitosis is a process of cell division where a single cell divides into two identical daughter cells. The major purpose of mitosis is for growth and to replace worn-out cells. Mitosis is divided into five phases: interphase, prophase, metaphase, anaphase, and telophase.
During interphase, the DNA in the cell is copied in preparation for cell division, resulting in two identical full sets of chromosomes. Outside of the nucleus are two centrosomes, each containing a pair of centrioles that are critical for the process of cell division.
During prophase, the chromatin condenses into discrete chromosomes. The mitotic spindle extends across the cell between the centrioles as they move to opposite poles of the cell. In metaphase, the chromosomes line up neatly end-to-end along the center (equator) of the cell.
In anaphase, each chromatid separates at its centromere and migrates to opposite poles of the cell. Finally, during telophase at each pole of the cell, a full set of chromosomes gather together, and a membrane form around each set.
Mitosis is important because it allows organisms to grow and repair damaged tissues by replacing old or dead cells with new ones that are genetically identical to their parent cells. Mistakes made during mitosis can result in changes in DNA that can potentially lead to genetic disorders if not corrected in time.
Mitosis is different from meiosis which involves two rounds of nuclear division resulting in four daughter cells with half as many chromosomes as their parent cells. Meiosis produces genetically diverse offspring while mitosis produces genetically identical offspring.
An Alternative Path: G0 Phase
The G0 phase, also known as the resting phase, is a cellular state outside of the replicative cell cycle. During this phase, a cell is neither dividing nor preparing to divide. Many cells spend most of their time in this phase either at rest or performing assigned duties.
The cell performs regulatory and basic cellular functions during this period. Cells in the G0 phase are not actively preparing to divide. The cell is in a quiescent (inactive) stage that occurs when cells exit the cell cycle.
The G0 phase is important for tissue stem cells to respond quickly to stimuli and maintain proper homeostasis and regeneration.
Reversible G0 phases can also be found in non-stem cells such as mature hepatocytes. In muscle stem cells, mTORC1 activity has been identified to control the transition from G0 into GAlert along with signaling through the HGF receptor cMet.
The transition from G1 to S phase is promoted by the inactivation of Rb through its progressive hyperphosphorylation by the Cyclin D/Cdk4 and Cyclin E/Cdk2 complexes in late G1.
An early observation that loss of Rb promoted cell cycle re-entry in G0 cells suggested that Rb is also essential in cells lacking cdk3 but functional in cdk4.
Cell Cycle Regulation
Cell division is essential for the growth, maintenance, and repair of cells and tissues in multicellular organisms. The cell cycle consists of the interphase and the mitotic phase. During interphase, the cell grows, and the nuclear DNA is duplicated.
In contrast, during the mitotic phase, replicated DNA and cytoplasmic material are divided into two identical cells. Cell division is tightly regulated because an occasional failure of regulation can have life-threatening consequences.
Most somatic cells divide regularly except for a few cells in the body that do not undergo cell division. Somatic cells are general terms for body cells. All human cells except for germ cells that produce eggs and sperm are somatic cells. Germ cells undergo meiosis to produce gametes with half the number of chromosomes as somatic cells.
The molecular regulators of the mitosis/meiosis decision have been discovered in most major model multicellular organisms over the past decade.
Careful regulation of the cell cycle is important to multicellular organisms to ensure that next-generation cells are proper and have a high survival rate facing different conditions. When cell division could not be regulated, it could affect the whole system to go off.
Cell Cycle Examples
Cell division is a fundamental process that allows organisms to grow, repair, and reproduce. In unicellular organisms such as bacteria and yeasts, cell division produces a completely new organism.
In multicellular organisms, individual cells grow and divide via a process called mitosis, allowing the organism to grow. The cell cycle is tightly regulated because the occasional failure of regulation can have life-threatening consequences.
New blood and skin cells are constantly being produced in humans through cell division for the growth and maintenance and repair of cells and tissues.
All multicellular organisms use cell division for these purposes. Somatic cells are body cells that regularly divide except for the cells that produce eggs and sperm which are referred to as germ cells.
Mitosis is a process in which DNA condenses to form short, tightly coiled-chromosomes. Each chromosome then splits longitudinally forming two identical chromatids. Each pair of chromatids attaches to spindle fibers which pull them apart during anaphase.
The attached chromatids move toward the spindle poles where they unravel to form new nuclei. After mitosis comes cytokinesis, the division of the cytoplasm into two identical daughter cells.
p53
The p53 gene provides instructions for making a protein called tumor protein p53 (or p53), which acts as a tumor suppressor. The p53 protein is a regulatory protein that plays a crucial role in preventing the formation of tumors.
Mutations or changes in the p53 gene may cause cancer cells to grow and spread in the body, and these changes have been found in a genetic condition called Li-Fraumeni syndrome. The p53 gene is the most frequently altered gene in human cancers.
Cyclins
Cyclins are a family of proteins that regulate the progression of a cell through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes.
CDKs are serine/threonine kinases that are key regulatory enzymes involved in cell proliferation by regulating cell-cycle checkpoints and transcriptional events in response to extracellular signals. Cyclins bind to CDKs, activate them, and provide substrate specificity for their catalytic partner serine-threonine kinases.
Several classes of cyclins have been described in mammalian cells, designated A to I, and also T. During the mitotic cell cycle, cyclins from the D-type family (D1, D2, and D3) regulate the progression of cells through the G1 phase.
Cyclin D-Cdk4/6 complexes phosphorylate retinoblastoma protein (Rb), which releases E2F transcription factors from Rb-E2F complexes and promotes entry into the S phase. Cyclin A is required for DNA replication during the S phase and is degraded at the end of mitosis. Cyclin B is required for entry into mitosis and is degraded at the end of mitosis.
Cyclins play an important role in cancer biology. The overexpression or amplification of cyclins leading to various breast cancer phenotypes has been reported.
Cyclin/Cyclin-dependent kinases (CDK) prevent the cell from moving on to the next checkpoint in response to DNA damage. The cyclin/CDKs themselves are negatively regulated by cyclin-dependent kinase inhibitors (CKIs).
Cyclin-Dependent Protein Kinases
Cyclin-dependent kinases (CDKs) are protein kinases that play important roles in the control of cell division and modulate transcription in response to several extra- and intracellular cues. CDKs require a separate subunit, a cyclin, that provides domains essential for enzymatic activity.
The evolutionary expansion of the CDK family in mammals led to the division of CDKs into three cell-cycle-related subfamilies (Cdk1, Cdk4, and Cdk5) and five transcriptional subfamilies (Cdk7, Cdk8, Cdk9, Cdk11, and Cdk20).
CDKs are involved in critical cellular processes such as cell cycle or transcription whose activity requires precise regulation. They modify various protein substrates involved in cell cycle progression by phosphorylating them.
CDKs require the presence of cyclins to become active. Cyclins activate CDKs by binding to them. All eukaryotes have multiple cyclins, each of which acts during a specific stage of the cell cycle. In organisms with multiple CDKs, each CDK is paired with a specific cyclin.
The regulation of CDK activity involves several mechanisms such as the binding of regulatory inhibitory phosphorylation and the binding of CDK inhibitory subunits (CKIs).
Full kinase activity requires activating phosphorylation on a threonine adjacent to the CDK’s active site. Unlike activating phosphorylation, CDK inhibitory phosphorylation is vital for regulating the cell cycle.
Maturation-Promoting Factor
Maturation-promoting factor (MPF) is a protein complex that regulates the passage of a cell from the G2 growth phase to the M phase. MPF is composed of a complex between p34cdc 2 protein kinase and a B-type cyclin.
The primary function of MPF is to stimulate the mitotic and meiotic phases of the cell cycle, promoting the entrance into mitosis (the M phase) from interphase. MPF causes cells to enter M-phase upon microinjection and will induce metaphase in nuclei incubated in cell extracts.
Activation of MPF is required for the cell to transition from G2 to the M phase. There are three amino acid residues responsible for this G2 to the M phase transition. The Threonine-161 (Thr-161) on CDK1 must be phosphorylated by a CDK-activating kinase (CAK).
CAK only phosphorylates Thr-161 when cyclin B is now free and can bind to cyclin B, activate MPF, and make the cell enter mitosis.
MPF plays an essential role in regulating the cell cycle. It causes cells to enter M-phase, which is necessary for proper cellular division. Without MPF, cells would not be able to divide properly, leading to various health problems.
Anaphase-Promoting Complex/Cyclosome
The anaphase-promoting complex or cyclosome (APC/C) is a large multi-subunit cullin-RING E3 ubiquitin ligase that controls sister chromatid segregation and the exit from mitosis by catalyzing the ubiquitylation of cyclins and other cell cycle regulatory proteins.
The APC/C targets specific substrates for degradation by the 26S proteasome. It has essential functions in and outside the eukaryotic cell cycle.
The APC/C recognizes its substrates through complex mechanisms for substrate recognition, and a universal mode of APC/C-substrate recognition does not exist.
The classical APC/C degron is the destruction box or D box, which is present in many substrates. Another motif recognized by the APC/C is the KEN box, which is present in some substrates.
The regulation of Cdc20 proteolysis reveals a role for APC components Cdc23 and Cdc27 during the S phase and early mitosis. The Polo-like kinase Cdc5p and the WD-repeat protein Cdc20p/Fizzy are regulators and substrates of the anaphase-promoting complex in Saccharomyces cerevisiae.
Apc15 plays an important role in APC/CCdc20 activation following the bi-orientation of sister chromatids across the metaphase plate.
When kinetochores are unattached to spindles, mitotic checkpoint complexes (MCC) inhibit APC. In the absence of Apc15, MCCs, and Cdc20 remain locked on.
