S-phase-promoting factor

Last updated
  1. Introduction:
    1. S-phase-promoting factor(SPF) is varying Cdk/cyclin complexes in eukaryotes that initiates the S-phase in the cell cycle. [1] SPF is at its peak when the cell cycle is transiting from G1 phase to the S-phase. [1] The SPF is at its lowest during the cell cycle once the cyclin subunits are used up, and broken down. [1] Therefore, everything that happens during mitosis is irreversible, which is why there are many steps within the cell cycle. [1] However, these steps are irreversible because one is needed in order for the next step to occur. [1]
  2. Control of S-phase-promoting factor:
    1. The S-phase-promoting factor is controlled by regulating cyclins levels, and by inhibitors seen in the other phases, such as G1. [1] One specific inhibitor seen in G1 is known as stoichiometric inhibitors, and causes the inhibition of cdk/cyclin complexes. [1] Regulating cyclin levels is done by the production and destruction of cyclin, which is done through the phosphorylation and dephosphorylation of anaphase-promoting complex (APC). [1] This controls the rate of production of cyclin, and regulates cyclin levels and controls the S-phase-promoting factor. [1]
  3. S-phase:
    1. During cell replication when DNA is replicated, and is initiated by the S-phase-promoting factor(SPF) cyclin complexes. [2] The DNA replication takes place, due to the increase in SPF during the switching from G1 to S phase in the cell cycle. [2] SPF is also used to inhibit double replication of chromosomes  in the cell cycle, which is important for not allowing a duplication of our genome to occur. [2]
  4. Cyclins:
    1. There are a variety of cyclins that can be found, and vary based on the type of eukaryotic cell. However, there are two cyclins that are found in all eukaryotes. [2] The presence of cyclin-CDK is crucial for the replication of DNA to occur in the S-phase. [2]
    2. Through different studies done on the effects and contributions to DNA replication, it is clear that certain cyclins hold significant influences over SPF activity. [3] For instance, there was a particular study done on the activity of Xenopus eggs. [3] This research indicated the importance of cyclins A, E and B in regards to the activity of SPF. It was concluded that there was more influence over the activity of SPF with different combinations of cyclins A and E, whereas there was not for cyline B. [3] Specifically, different concentrations contributed to the activity of SPF, which affects DNA replication. Having high concentration of cyclin A within the cell cycle causes mitosis to occur, which directly affects DNA replication by being inhibited. [3]   Therefore, the type of cyclins and their concentrations have a direct effect on the activity of SPF when in S-phase, which has an effect on DNA replication. [3]
CyclinsSpecies
cyclin E (cycE)-Cdk2, cycA-Cdk2, and cycA-Cdc2 kinasesHumans, frogs and flies
Clb5p-Cdc28p, Clb6p-Cdc28p, and cig2-cdc2Yeast

The table conveys different eukaryotes, and Cyclin-CDK complexes needed for the species to initiate DNA replication, which occurs in the S-phases. [2]

Related Research Articles

<span class="mw-page-title-main">Cell cycle</span> Series of events and stages that result in cell division

The cell cycle, or cell-division cycle, is the series of events that take place in a cell that causes it to divide into two daughter cells. These events include the duplication of its DNA and some of its organelles, and subsequently the partitioning of its cytoplasm, chromosomes and other components into two daughter cells in a process called cell division.

<span class="mw-page-title-main">Cell division</span> Process by which living cells divide

Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there are two distinct types of cell division: a vegetative division (mitosis), producing daughter cells genetically identical to the parent cell, and a cell division that produces haploid gametes for sexual reproduction (meiosis), reducing the number of chromosomes from two of each type in the diploid parent cell to one of each type in the daughter cells. In Mitosis is a part of the cell cycle, in which, replicated chromosomes are separated into two new nuclei. Cell division gives rise to genetically identical cells in which the total number of chromosomes is maintained. In general, mitosis is preceded by the S stage of interphase and is followed by telophase and cytokinesis; which divides the cytoplasm, organelles, and cell membrane of one cell into two new cells containing roughly equal shares of these cellular components. The different stages of mitosis all together define the M phase of an animal cell cycle—the division of the mother cell into two genetically identical daughter cells. To ensure proper progression through the cell cycle, DNA damage is detected and repaired at various checkpoints throughout the cycle. These checkpoints can halt progression through the cell cycle by inhibiting certain cyclin-CDK complexes. Meiosis undergoes two divisions resulting in four haploid daughter cells. Homologous chromosomes are separated in the first division of meiosis, such that each daughter cell has one copy of each chromosome. These chromosomes have already been replicated and have two sister chromatids which are then separated during the second division of meiosis. Both of these cell division cycles are used in the process of sexual reproduction at some point in their life cycle. Both are believed to be present in the last eukaryotic common ancestor.

G<sub>1</sub> phase First growth phase in the eukaryotic cell cycle

The G1 phase, gap 1 phase, or growth 1 phase, is the first of four phases of the cell cycle that takes place in eukaryotic cell division. In this part of interphase, the cell synthesizes mRNA and proteins in preparation for subsequent steps leading to mitosis. G1 phase ends when the cell moves into the S phase of interphase. Around 30 to 40 percent of cell cycle time is spent in the G1 phase.

<span class="mw-page-title-main">Anaphase-promoting complex</span> Cell-cycle regulatory complex

Anaphase-promoting complex is an E3 ubiquitin ligase that marks target cell cycle proteins for degradation by the 26S proteasome. The APC/C is a large complex of 11–13 subunit proteins, including a cullin (Apc2) and RING (Apc11) subunit much like SCF. Other parts of the APC/C have unknown functions but are highly conserved.

<span class="mw-page-title-main">Cyclin</span> Group of proteins

Cyclin is a family of proteins that controls the progression of a cell through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes or group of enzymes required for synthesis of cell cycle.

<span class="mw-page-title-main">S phase</span> DNA replication phase of the cell cycle, between G1 and G2 phase

S phase (Synthesis phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during S-phase are tightly regulated and widely conserved.

G<sub>2</sub> phase Second growth phase in the eukaryotic cell cycle, prior to mitosis

G2 phase, Gap 2 phase, or Growth 2 phase, is the third subphase of interphase in the cell cycle directly preceding mitosis. It follows the successful completion of S phase, during which the cell’s DNA is replicated. G2 phase ends with the onset of prophase, the first phase of mitosis in which the cell’s chromatin condenses into chromosomes.

<span class="mw-page-title-main">Restriction point</span> Animal cell cycle checkpoint

The restriction point (R), also known as the Start or G1/S checkpoint, is a cell cycle checkpoint in the G1 phase of the animal cell cycle at which the cell becomes "committed" to the cell cycle, and after which extracellular signals are no longer required to stimulate proliferation. The defining biochemical feature of the restriction point is the activation of G1/S- and S-phase cyclin-CDK complexes, which in turn phosphorylate proteins that initiate DNA replication, centrosome duplication, and other early cell cycle events. It is one of three main cell cycle checkpoints, the other two being the G2-M DNA damage checkpoint and the spindle checkpoint.

<span class="mw-page-title-main">Cell cycle checkpoint</span> Control mechanism in the eukaryotic cell cycle

Cell cycle checkpoints are control mechanisms in the eukaryotic cell cycle which ensure its proper progression. Each checkpoint serves as a potential termination point along the cell cycle, during which the conditions of the cell are assessed, with progression through the various phases of the cell cycle occurring only when favorable conditions are met. There are many checkpoints in the cell cycle, but the three major ones are: the G1 checkpoint, also known as the Start or restriction checkpoint or Major Checkpoint; the G2/M checkpoint; and the metaphase-to-anaphase transition, also known as the spindle checkpoint. Progression through these checkpoints is largely determined by the activation of cyclin-dependent kinases by regulatory protein subunits called cyclins, different forms of which are produced at each stage of the cell cycle to control the specific events that occur therein.

<span class="mw-page-title-main">G1/S transition</span> Stage in cell cycle

The G1/S transition is a stage in the cell cycle at the boundary between the G1 phase, in which the cell grows, and the S phase, during which DNA is replicated. It is governed by cell cycle checkpoints to ensure cell cycle integrity and the subsequent S phase can pause in response to improperly or partially replicated DNA. During this transition the cell makes decisions to become quiescent, differentiate, make DNA repairs, or proliferate based on environmental cues and molecular signaling inputs. The G1/S transition occurs late in G1 and the absence or improper application of this highly regulated checkpoint can lead to cellular transformation and disease states such as cancer.

Cyclin A is a member of the cyclin family, a group of proteins that function in regulating progression through the cell cycle. The stages that a cell passes through that culminate in its division and replication are collectively known as the cell cycle Since the successful division and replication of a cell is essential for its survival, the cell cycle is tightly regulated by several components to ensure the efficient and error-free progression through the cell cycle. One such regulatory component is cyclin A which plays a role in the regulation of two different cell cycle stages.

<span class="mw-page-title-main">Cell division cycle 7-related protein kinase</span> Protein-coding gene in the species Homo sapiens

Cell division cycle 7-related protein kinase is an enzyme that in humans is encoded by the CDC7 gene. The Cdc7 kinase is involved in regulation of the cell cycle at the point of chromosomal DNA replication. The gene CDC7 appears to be conserved throughout eukaryotic evolution; this means that most eukaryotic cells have the Cdc7 kinase protein.

<span class="mw-page-title-main">Wee1</span> Nuclear protein

Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe. Wee1 has a molecular mass of 96 kDa and is a key regulator of cell cycle progression. It influences cell size by inhibiting the entry into mitosis, through inhibiting Cdk1. Wee1 has homologues in many other organisms, including mammals.

A series of biochemical switches control transitions between and within the various phases of the cell cycle. The cell cycle is a series of complex, ordered, sequential events that control how a single cell divides into two cells, and involves several different phases. The phases include the G1 and G2 phases, DNA replication or S phase, and the actual process of cell division, mitosis or M phase. During the M phase, the chromosomes separate and cytokinesis occurs.

<span class="mw-page-title-main">Control of chromosome duplication</span>

In cell biology, eukaryotes possess a regulatory system that ensures that DNA replication occurs only once per cell cycle.

<span class="mw-page-title-main">G2-M DNA damage checkpoint</span>

The G2-M DNA damage checkpoint is an important cell cycle checkpoint in eukaryotic organisms that ensures that cells don't initiate mitosis until damaged or incompletely replicated DNA is sufficiently repaired. Cells with a defective G2-M checkpoint will undergo apoptosis or death after cell division if they enter the M phase before repairing their DNA. The defining biochemical feature of this checkpoint is the activation of M-phase cyclin-CDK complexes, which phosphorylate proteins that promote spindle assembly and bring the cell to metaphase.

Clb5 and Clb6 are B-type, S-phase cyclins in yeast that assist in cell cycle regulation. Clb5 and Clb6 bind and activate Cdk1, and high levels of these cyclins are required for entering S-phase. S-phase cyclin binding to Cdk1 directly stimulates DNA replication as well as progression to the next phase of the cell cycle.

<span class="mw-page-title-main">DNA re-replication</span> Undesirable occurrence in eukaryotic cells

DNA re-replication is an undesirable and possibly fatal occurrence in eukaryotic cells in which the genome is replicated more than once per cell cycle. Rereplication is believed to lead to genomic instability and has been implicated in the pathologies of a variety of human cancers. To prevent rereplication, eukaryotic cells have evolved multiple, overlapping mechanisms to inhibit chromosomal DNA from being partially or fully rereplicated in a given cell cycle. These control mechanisms rely on cyclin-dependent kinase (CDK) activity. DNA replication control mechanisms cooperate to prevent the relicensing of replication origins and to activate cell cycle and DNA damage checkpoints. DNA rereplication must be strictly regulated to ensure that genomic information is faithfully transmitted through successive generations.

Whi5 is a transcriptional regulator in the budding yeast cell cycle, notably in the G1 phase. It is an inhibitor of SBF, which is involved in the transcription of G1-specific genes. Cln3 promotes the disassociation of Whi5 from SBF, and its disassociation results in the transcription of genes needed to enter S phase.

The Neuronal cell cycle represents the life cycle of the biological cell, its creation, reproduction and eventual death. The process by which cells divide into two daughter cells is called mitosis. Once these cells are formed they enter G1, the phase in which many of the proteins needed to replicate DNA are made. After G1, the cells enter S phase during which the DNA is replicated. After S, the cell will enter G2 where the proteins required for mitosis to occur are synthesized. Unlike most cell types however, neurons are generally considered incapable of proliferating once they are differentiated, as they are in the adult nervous system. Nevertheless, it remains plausible that neurons may re-enter the cell cycle under certain circumstances. Sympathetic and cortical neurons, for example, try to reactivate the cell cycle when subjected to acute insults such as DNA damage, oxidative stress, and excitotoxicity. This process is referred to as “abortive cell cycle re-entry” because the cells usually die in the G1/S checkpoint before DNA has been replicated.

References

  1. 1 2 3 4 5 6 7 8 9 Kapuy, Orsolya; He, Enuo; López-Avilés, Sandra; Uhlmann, Frank; Tyson, John J.; Novák, Béla (2009-12-17). "System-level feedbacks control cell cycle progression". FEBS Letters. 583 (24): 3992–3998. doi:10.1016/j.febslet.2009.08.023. PMC   3811919 . PMID   19703449.
  2. 1 2 3 4 5 6 Nougarède, Romain; Della Seta, Flavio; Zarzov, Patrick; Schwob, Etienne (June 2000). "Hierarchy of S-Phase-Promoting Factors: Yeast Dbf4-Cdc7 Kinase Requires Prior S-Phase Cyclin-Dependent Kinase Activation". Molecular and Cellular Biology. 20 (11): 3795–3806. doi:10.1128/mcb.20.11.3795-3806.2000. ISSN   0270-7306. PMC   85702 . PMID   10805723.
  3. 1 2 3 4 5 Strausfeld, U.P.; Howell, M.; Descombes, P.; Chevalier, S.; Rempel, R.E.; Adamczewski, J.; Maller, J.L.; Hunt, T.; Blow, J.J. (1996-06-01). "Both cyclin A and cyclin E have S-phase promoting (SPF) activity in Xenopus egg extracts" . Journal of Cell Science. 109 (6): 1555–1563. doi:10.1242/jcs.109.6.1555. ISSN   1477-9137. PMID   8799842.

See also