The cell cycle or cell division cycle is a sequence of events occurring in a cell leading to its DNA division and duplication (DNA replication) to produce two daughter cells. In bacteria, which have no cell nucleus, the cell cycle is divided into periods B, C, and D. Period B extends from the end of cell division to the beginning of DNA replication. DNA replication occurs during period C. Period D refers to the stage between the end of DNA replication and the separation of bacterial cells into two daughter cells. In cells with nuclei, as in eukaryotes, the cell cycle is also divided into three periods: interphase, mitotic phase (M), and cytokinesis. During interphase, the cell grows, collects the nutrients needed for mitosis, prepares it for large cell division and duplicates its DNA. During the mitotic phase, the chromosomes are separated. During the final stages, the cytokinesis, chromosomes and cytoplasm separate into two new daughter cells. To ensure proper cell division, there is a control mechanism known as cell cycle checks. It helps the cells produce more
The cell division cycle is a vital process in which a single cell-fertilized egg develops into an adult organism, as well as a process in which hair, skin, blood cells, and some internal organs are renewed. After cell division, each child cell begins the interphase of the new cycle. Although the various stages of the interphase are usually indistinguishable morphologically, each phase of the cell cycle has a series of specialized biochemical processes that prepare cells to initiate cell division.
Video Cell cycle
Phase
The cell cycle consists of four distinct phases: phase G 1 , phase S (synthesis), phase G 2 (collectively known as interphase) and phase M (mitosis). Phase M itself consists of two very intense processes: karyokinesis, in which the cell chromosomes are divided, and the cytokinesis, in which the cell cytoplasm divides into two daughter cells. The activation of each phase depends on the correct development and completion of the previous one. Cells that temporarily or reversibly stop dividing are said to have entered a stationary state called the phase G 0 .
After cell division, each child cell begins the interphase of the new cycle. Although the various stages of interphase are usually indistinguishable morphologically, each phase of the cell cycle has a series of specialized biochemical processes that prepare cells for initiation of cell division. phases
G 0 (quiescence)
G 0 is the resting phase in which the cell has left the cycle and stops splitting. The cell cycle begins with this phase. The word "post-mitotic" is sometimes used to refer to silent and senescent cells. The non-proliferative (non-limiting) cells in multicellular eukaryotes generally enter the silent G 0 state of G 1 and can remain stationary for long periods of time, possibly indefinitely as is often the case for neurons). This is very common for completely differentiated cells. Cell aging occurs in response to DNA damage and external pressure and is usually an arrest in G 1 . Some cells enter the semi-permanent G 0 phase and are considered post-mitotic, for example, some liver cells, kidneys, and stomach. Many cells exclude G 0 and continue to divide throughout the life of the organism, such as epithelial cells.
Cell aging is also a situation that occurs in response to DNA damage or degradation that will make the offspring of the cell inanimate; is often a biochemical alternative to the destruction of damaged cells by apoptosis. Interphase (intermitosis)
Before the cell can enter cell division, need to take nutrients. All preparations are made during the interphase. Interphase is a series of changes that occur in newly formed cells and essentially, before becoming able to divide again. This is also called the preparation phase or intermitosis. Previously called the break stage because there is no clear activity associated with cell division. Usually the interfase takes at least 91% of the total time required for the cell cycle.
The interphase takes place in three stages, G 1 , S, and G 2 , followed by the cycle of mitosis and cytokinesis. The DNA content of the cell nucleus is duplicated during the S phase but can continue up to G 2 in the case of heterochromatin. phases
G 1 (First growth phase or Post mitotic fault phase)
The first phase in the interphase, from the end of the previous M phase to the beginning of DNA synthesis, is called G 1 (G denotes slit ). This is also called the growth phase. During this phase, cell biosynthetic activity, which is greatly slowed during phase M, continues at a high level. The duration of G 1 varies greatly, even among the different cells of the same species. In this phase, the cells increase their protein supply, increasing the number of organelles (such as mitochondria, ribosomes), and growing in size. In phase G 1 , the cell has three options. (1) To continue the cell cycle and enter the phase S (2) Stop the cell cycle and enter the phase G 0 to undergo differentiation. (3) Get catch in phase G 1 so it can enter the phase G 0 or re-enter the cell cycle. The decisive factor is the availability of nitrogen and the storage of energy-rich compounds at the so-called check point. This check point is called a restriction point or START and is set by G 1 /S cyclins, which causes the transition from G 1 to phase S. Section via checkpoint G 1 performs cells for division.
Phase S (DNA replication)
The next phase S begins when DNA synthesis begins; when completed, all chromosomes have been replicated, that is, each chromosome has two chromatids (sisters). Thus, during this phase, the amount of DNA in the cell has doubled, although the cell ploidies remain the same. The level of RNA transcription and protein synthesis is very low during this phase. The exception to this is the production of histones, most of which occur during the S phase. Phase
G 2 (growth)
G2 phase occurs after DNA replication and is a period of protein synthesis and rapid cell growth to prepare cells for mitosis. During this phase microtubules begin to rearrange to form spindles.
The mitotic phase (chromosomal separation)
The relatively short M phase consists of the nuclear division (karyokinesis). This is a relatively short period of cell cycle. M phase is very complex and very regular. The sequence of events is divided into phases, in accordance with the completion of a set of activities and the beginning of the next. This phase is sequentially known as:
- profase,
- metaphase,
- anafase,
- telophase
Mitosis is a process in which eukaryotic cells separate chromosomes in their cell nuclei into two identical sets in two nuclei. During the mitosis process the pairs of chromosomes condense and stick to the fibers that pull your chromatid to the opposite side of the cell.
Mitosis occurs exclusively in eukaryotic cells, but occurs in different ways in different species. For example, animals experience an "open" mitosis, where nuclear envelopes burst before chromosomes separate, while fungi such as Aspergillus nidulans and Saccharomyces cerevisiae (yeast) undergo "closed" mitosis where the chromosomes divide in the whole cell nucleus. Prokaryotic cells, which lack the core, are divided by a process called binary division.
Phase cytokinesis (segregation of all cell components)
Mitosis is immediately followed by cytokinesis, which divides nuclei, cytoplasm, organelle, and cell membrane into two cells containing more or less the same part of this cellular component. Mitosis and cytokinesis together define the distribution of stem cells into two child cells, which are genetically identical to each other and with their parent cells. It accounts for about 10% of the cell cycle.
Because cytokinesis usually occurs simultaneously with mitosis, "mitosis" is often used interchangeably with "phase M". However, there are many cells in which mitosis and cytokinesis occur separately, forming single cells with many nuclei in a process called endorepepsy. This occurs mainly among mushrooms and slime mold, but is found in various groups. Even in animals, cytokinesis and mitosis can occur independently, for example during certain stages of embryo development of the fly. Mistakes in mitosis can kill cells through apoptosis or cause mutations that can cause cancer.
The process of mitosis is very complicated and very regular. The sequence of events is divided into phases, in accordance with the completion of a set of activities and the beginning of the next. These stages are prophase, prometafase, metaphase, anaphase and telophase. During the mitosis process the pairs of chromosomes condense and stick to the fibers that pull your chromatid to the opposite side of the cell. The cell is then divided into cytokinesis, to produce two identical daughter cells.
Maps Cell cycle
Eukaryotic cell cycle setting
The regulation of the cell cycle involves processes that are essential for cell survival, including detection and repair of genetic defects and the prevention of uncontrolled cell division. Molecular events that control the cell cycle are sequential and directed; that is, every process occurs sequentially and it is not possible to "reverse" the cycle.
Role of cyclins and CDK
The two main classes of regulating molecules, cyclic and cyclic dependent cycles (CDK), determine cell progression through the cell cycle. Leland H. Hartwell, R. Timothy Hunt, and Paul M. Nurse won the 2001 Nobel Prize in Physiology or Medicine for the discovery of these central molecules. Many genes that encode cyclometers and CDKs are preserved among all eukaryotes, but in general more complex organisms have more complex cell cycle control systems that incorporate more individual components. Many of the relevant genes were first identified by studying yeast, especially Saccharomyces cerevisiae ; the genetic nomenclature in yeasts emits many of these genes cdc (for "cell division cycle") followed by identification number, for example cdc25 or cdc20 .
Cyclins form the regulatory subunits and CDK of the catalytic subunits of activated heterodimers; the cyclometer has no catalytic activity and the CDK is inactive in the absence of partner cyclin. When activated by a cyclic bound, the CDK performs a common biochemical reaction called phosphorylation that activates or disables the target protein to set coordinated entries to the next phase of the cell cycle. Different cyclin-CDK combinations determine targeted downstream proteins. CDK is constitutively expressed in cells while the cyclical is synthesized at specific stages of the cell cycle, in response to various molecular signals.
Common mechanism of cyclin-CDK interaction
After receiving a pro-mitotic extracellular signal, the cyclic-CDK complex G 1 becomes active to prepare cells for the S phase, promoting the expression of transcription factors which in turn promotes the expression of S cyclin and enzymes. needed for DNA replication. The cyclin-CDK G 1 complex also promotes molecular degradation that acts as a S phase inhibitor by targeting them for ubiquitination. Once the protein has been ubiquitinated, it is targeted for proteolytic degradation by proteasome. However, results from recent studies on the dynamics of E2F transcription at a single cell level argue that the role of G1 cyclin-CDK activity, in particular the D-CDK4/6 cyclin, is to adjust time rather than commitment to cell cycle entries.
The S cyclin-CDK complex is an active phosphorylate protein that forms a pre-replicated complex assembled during the G 1 phase at the origin of DNA replication. Phosphorylation serves two purposes: to activate every pre-replicated complex that has been assembled, and to prevent the formation of new complexes. This ensures that every part of the cell genome will be replicated once and only once. The reason for preventing the gaps in replication is quite clear, because the child cells that are missing all or some of the important genes will die. However, for reasons related to the effect of numbered copies of genes, possession of additional copies of certain genes also damages the daughter cells.
The mitotic cyclin-CDK complex, synthesized but inactive during the S and G 2 phases, promotes mitotic initiation by stimulating downstream proteins involved in chromosomal condensation and mitotic spindle assembly. A critical complex that is activated during this process is the ubiquitin ligage known as the anaphase-promoting complex (APC), which promotes degradation of structural proteins associated with the kinetocor chromosome. APC also targets mitotic cyclins for degradation, ensuring that telofase and cytokinesis can be continued.
Cyclin-CDK complex specific actions
Cyclin D is the first cyclin produced in the cell cycle, in response to extracellular signals (eg growth factors). Cyclin D binds to existing CDK4, forming an active D-CDK4 cyclin complex. The Cyclin D-CDK4 complex in turn phosphorylates the protein susceptibility of retinoblastoma (Rb). The hyperphosphorylated Rb separates itself from the E2F/DP1/Rb complex (which binds to the E2F responsive gene, effectively "blocking" them from transcription), activating E2F. E2F activation results in the transcription of various genes such as cyclin E, cyclin A, DNA polymerase, thymidine kinase, etc. Cyclin E thus produced binds to CDK2, forming the cyclic complex E-CDK2, which drives cells from G 1 to the S (G 1 /S phase, which begins the transition G 2 /M). The activation of the Cyclin B-cdk1 complex causes nuclear envelope interference and prophase initiation, and then, deactivation causes the cell to escape mitosis. A quantitative study of the dynamics of E2F transcription at a single cell level using engineered fluorescent reporter cells provides a quantitative framework for understanding the logic of control cell cycle entries, challenging the canonical book model. The gene that governs the accumulated E2F accumulation, such as Myc, determines commitment in cell cycle and phase entry S. Activity G1 cyclin-CDK is not the driver of cell cycle entries. Instead, they mainly regulate the increased time of E2F, thereby modulating the rate of cell cycle development.
Inhibitor
Two families of genes, family of kip/kip (protein CDK interacting proteins/Kinase inhibiting proteins ) and INK4a/ARF ( In hibitor of K inase 4/ A lternative R issues the family F ), preventing the development of the cell cycle. Because these genes play a role in the prevention of tumor formation, they are known as tumor suppressors.
cip/kip family includes genes p21, p27 and p57. They stop the cell cycle in phase G 1 , by binding, and disabling, cyclin-CDK complex. p21 is activated by p53 (which, in turn, is triggered by DNA damage eg due to radiation). p27 is enabled by Transforming Growth Factor? (TGF?), Growth inhibitors.
The INK4a/ARF family includes p16 INK4a , which binds to CDK4 and holds the cell cycle in G 1 phase, and p14 ARF that prevents p53 degradation.
A synthetic inhibitor of Cdc25 may also be useful for cell cycle capture and is therefore useful as an antineoplastic and anticancer agent.
Network of transcription settings
Current evidence suggests that semi-autonomous transcription networks act in conjunction with CDK-cyclin machines to regulate cell cycles. Several studies of gene expression in Saccharomyces cerevisiae have identified 800-1200 genes that alter expression during cell cycle. They are transcribed at high levels at certain points in the cell cycle, and remain at a lower level throughout the rest of the cycle. While the set of genes identified differed between studies due to computational methods and the criteria used to identify them, each study showed that most yeast genes were regulated temporally.
Many genes expressed periodically are driven by transcription factors that are also expressed periodically. A single-gene KO-scan screen identifies 48 transcription factors (about 20% of all non-essential transcription factors) that indicate the developmental defects of the cell cycle. Genome-wide studies using high throughput technology have identified a transcription factor that binds yeast gene promoters, and linking these findings to patterns of temporal expression has enabled identification of transcription factors that promote phase-specific gene expression. The expression profile of this transcription factor is driven by transcription factors that peak in the previous phase, and the computational model has shown that the CDK-autonomic network of these transcription factors is sufficient to produce steady-state oscillations in gene expression).
Experimental evidence also suggests that gene expression may oscillate with periods seen in wild-type cell divide independently of CDK machines. Orlando et al. Using a microarray to measure the expression of a set of 1,271 genes that they identified as periodic in both wild-type cells and cells that lacked all S-phase and mitotic cyclins ( clb1,2,3,4,6,6 ). Of the 1,271 genes tested, 882 continues to be expressed in cyclic deficiency cells at the same time as wild-type cells, despite the fact that cyclin-deficient cells capture at the boundary between G 1 and the phases S. However, 833 genes tested changed behavior between wild and mutant cells, suggesting that these genes may be directly or indirectly regulated by CDK-cyclin machines. Some genes that continue to be expressed on time in mutant cells are also expressed at different levels in wild and mutant type cells. These findings suggest that while transcriptional tissues can oscillate separately from CDK-cyclin oscillators, they are combined in a way that requires both to ensure the exact time of the cell cycle events. Other work suggests that phosphorylation, post-translational modification, cell cycle transcription factors by Cdk1 may alter the localization or activity of the transcription factor to control the time of the target gene strictly.
While oscillating transcription plays a key role in the development of the yeast cell cycle, the CDK-cyclin machine operates independently in the early embryonic cell cycle. Before midblastula transition, zygotic transcription does not occur and all the required proteins, such as the B-type cyclic, are translated from mRNAs that are maternally loaded.
DNA replication and activity of DNA replication
Synchronized cultural analyzes of Saccharomyces cerevisiae under conditions that prevent the initiation of DNA replication without delaying the development of cell cycle suggest that the original licensing reduces the expression of genes with origin near their 3 'ends, revealing that the origin of the downstream can be regulate the expression of upstream genes. This confirms earlier predictions of mathematical modeling of global causal co-ordination between the activity of DNA replication and mRNA expression, and suggests that mathematical modeling of DNA microarray data can be used to precisely predict the previously unknown biological modes of regulation.
Checkpoints
Cell cycle checkpoints are used by cells to monitor and regulate the development of cell cycle. Checkpoints prevent the development of cell cycle at certain points, allowing verification of required phase processes and repair of DNA damage. Cells can not proceed to the next phase until the check point requirements have been met. The checkpoints usually consist of a network of regulating proteins that monitor and determine the development of cells through various stages of the cell cycle.
There are several checkpoints to ensure that damaged or incomplete DNA is not passed on to the child's cells. Three main checkpoints exist: checkpoint G 1 /S, checkpoint G 2 /M and metaphase check point (mitosis).
G 1 /S transition is a rate-limiting step in the cell cycle and is also known as a limiting point. This is where the cell checks whether it has enough raw materials to fully mimic DNA (nucleotide bases, DNA synthase, chromatin, etc.). Unhealthy or malnourished cells will be stuck at this checkpoint.
The G 2 /M checkpoint is where the cell ensures that it has enough cytoplasm and phospholipids for the two daughter cells. But sometimes more importantly, it checks to see if this is the right time to do the replication. There are situations where many cells need to replicate simultaneously (for example, a growing embryo must have a symmetrical cell distribution until it reaches the mid-blastula transition). This is done by controlling the checkpoint G 2 /M.
The metaphase check point is a small enough checkpoint, that once the cell is in metaphase, it has committed itself to undergoing mitosis. But that does not mean it does not matter. At this checkpoint, the cell checks to make sure that the spindle is formed and all chromosomes are aligned to the spindle equator before the anaphase begins.
Although these are the three "main" checkpoints, not all cells have to pass through each of these checkpoints in this order to be replicated. Many types of cancer are caused by mutations that allow cells to pass through various checkpoints or even miss them altogether. Go from S to M to S phase almost sequentially. Because these cells have lost their checkpoints, any DNA mutations that may have occurred are ignored and passed on to the daughter cells. This is one of the reasons why cancer cells have a tendency to grow exponentially. Aside from cancer cells, many completely different cell types no longer replicate so they leave the cell cycle and remain in G 0 until their death. Thereby eliminating the need for cellular checkpoints. An alternative model of cell cycle response to DNA damage has also been proposed, known as post-verification checkpoints.
The setting of checkpoints plays an important role in the development of the organism. In sexual reproduction, when egg-fertilization occurs, when the sperm binds the egg, it releases a signal that tells the fertilized egg. Among these, it induces the currently fertilized oocyte to return from the previously inactive, G 0 , back to the cell cycle and to the mitotic replication and division.
p53 plays an important role in triggering the control mechanisms at both G 1 /S and G 2 /M checkpoints. In addition to p53, checkpoint regulators are being studied in depth for their role in the growth and proliferation of cancer.
Cell cycle fluorescence imaging
The pioneering work by Atsushi Miyawaki and co-workers developed a cyclic ubiquitination-based cell cycle indicator (FUCCI), which allows cell cycle fluorescence imaging. Initially, the green fluorescent protein, mAG, fused with hGem (1/110) and orange fluorescent protein (mKO 2 ) were combined to hCdt1 (30/120). Note, this fusion is a fragment containing a nuclear localization signal and a ubiquitination site for degradation, but not a functional protein. The green fluorescent protein is made during S, G 2 , or phase M and is degraded during the G 0 or G 1 phase, while the orange fluorescent protein is made during phase G 0 or G 1 and destroyed during S, G 2 , or M. A FUCCI far-red and near-infrared was developed using fluorescent proteins derived from cyanobacteria (smURFP) and fluorescent proteins derived from bacteriophytochrome (the films found at this link).
Role in tumor formation
Disregulation of cell cycle components can lead to tumor formation. As mentioned above, when some genes such as cell cycle inhibitors, RB, p53 etc. mutate, they can cause cells to multiply uncontrollably, forming a tumor. Although the duration of the cell cycle in tumor cells is equal to or longer than the normal cell cycle, the proportion of cells that are in active cell division (compared to the cell diameter in G 0 phase) in the tumor is much higher than that in normal network. So there is a net increase in the number of cells because the number of cells that die by apoptosis or aging remains the same.
Cells that are actively undergoing cell cycles are targeted in cancer therapy because DNA is relatively open during cell division and therefore susceptible to damage by drugs or radiation. This fact is used in the treatment of cancer; by a process known as debulking, a significant mass of tumors is removed which drives a large number of remaining tumor cells from the G 0 phase to G 1 (due to increased availability of nutrients, oxygen, growth factors , etc.). Radiation or chemotherapy follows the debulking procedure of killing these cells that just enter the cell cycle.
The fastest cycling mammal cell in culture, crypt cells in the intestinal epithelium, has a cycle time as short as 9 to 10 hours. Stem cells in resting mice skin may have a cycle time of more than 200 hours. Much of this difference is due to the varying lengths of G 1 , the most varied cycle phases. M and S are not much different.
In general, most radiosensitive cells are in the final phase of M and G 2 and most resistant to the final S phase.
For cells with longer cell cycle times and very long G 1 phases, there is a second resistance peak at the end of G 1 .
The pattern of resistance and sensitivity correlates with the level of the sulfhydryl compound in the cell. Sulfhydryl is a natural substance that protects cells from radiation damage and tends to be at the highest level in S and at its lowest mitosis.
See also
- Mobile model
- Sync culture - cell culture sync
References
Further reading
External links
- This article incorporates public domain material from the NCBI document "Science Primer".
- David Morgan Seminar: Controlling the Cell Cycle
- Cell Cycle & amp; Cell death
- Transcription program from cell cycle: high resolution time
- The cell cycle and metabolic cycle govern transcription in yeast
- Animated Cycle Cell 1Lec.com
- Cell Cycle
- Fucci: Using GFP to visualize the cell cycle
- Science Creative Quarterly Summary about cell cycle
- KEGG - Human Cell Cycle
Source of the article : Wikipedia
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