anaphase: the stage of mitosis during which sister chromatids are separated from each other cell cycle: the ordered sequence of events that a cell passes through between one cell division and the next cell cycle checkpoints: mechanisms that monitor the preparedness of a eukaryotic cell to advance through the various cell cycle stages cell plate: a structure formed during plant-cell cytokinesis by Golgi vesicles fusing at the metaphase plate; will ultimately lead to formation of a cell wall to separate the two daughter cells centriole: a paired rod-like structure constructed of microtubules at the center of each animal cell centrosome cleavage furrow: a constriction formed by the actin ring during animal-cell cytokinesis that leads to cytoplasmic division cytokinesis: the division of the cytoplasm following mitosis to form two daughter cells G0 phase: a cell-cycle phase distinct from the G1 phase of interphase; a cell in G0 is not preparing to divide G1 phase: (also, first gap) a cell-cycle phase; first phase of interphase centered on cell growth during mitosis G2 phase: (also, second gap) a cell-cycle phase; third phase of interphase where the cell undergoes the final preparations for mitosis interphase: the period of the cell cycle leading up to mitosis; includes G1, S, and G2 phases; the interim between two consecutive cell divisions kinetochore: a protein structure in the centromere of each sister chromatid that attracts and binds spindle microtubules during prometaphase metaphase plate: the equatorial plane midway between two poles of a cell where the chromosomes align during metaphase metaphase: the stage of mitosis during which chromosomes are lined up at the metaphase plate mitosis: the period of the cell cycle at which the duplicated chromosomes are separated into identical nuclei; includes prophase, prometaphase, metaphase, anaphase, and telophase mitotic phase: the period of the cell cycle when duplicated chromosomes are distributed into two nuclei and the cytoplasmic contents are divided; includes mitosis and cytokinesis mitotic spindle: the microtubule apparatus that orchestrates the movement of chromosomes during mitosis prometaphase: the stage of mitosis during which mitotic spindle fibers attach to kinetochores prophase: the stage of mitosis during which chromosomes condense and the mitotic spindle begins to form quiescent: describes a cell that is performing normal cell functions and has not initiated preparations for cell division S phase: the second, or synthesis phase, of interphase during which DNA replication occurs telophase: the stage of mitosis during which chromosomes arrive at opposite poles, decondense, and are surrounded by new nuclear envelopes
This item was written in association with Dr Margarete Heck and her research group, The Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, UK.
A summary of ‘Cell cycle control’. The ‘life cycle’ of a dividing eukaryotic non-embryonic cell starts with the cell triggered to enter the cell cycle and ends with the equal partitioning of the genetic material and cleavage of the cell during cytokinesis. The whole process is called the cell cycle and consists of four main phases. Entry to the cycle is made in Gap 1 (G1) phase and this is followed in sequence by a DNA synthesis (S) phase, Gap 2 (G2) phase, and Mitosis (M). After mitosis (M) some cells enter the G1 phase of a new cell cycle whilst others may diverge at the start of G1 into a phase called Gap O (zero). Phases G1, S and G2 are often grouped and called ‘interphase’. Cells in G-0 (zero) are quiescent and not dividing (hence zero), this may be permanent or temporary. After cell division the daughter cells follow ONE of several pathways: Mitosis is visually very dramatic but it only occupies about 5% of the total cell cycle time. Within the ‘big picture’ of the life cycle of a dividing cell, interphase (phases G1, S, and G2) account for the other 95% of cell cycle time. Research evidence shows interphase (once called resting phase!) operates in a beautifully ordered systematic way. It has also been shown to be more complicated than previously thought. The time taken for a eukaryotic cell to divide varies widely with cell type and environment. Yeast cells take from 1.5 to 3 hours, intestinal epithelial cells about 12 hours and cells in culture about 22 hours. In different organisms and at different developmental times the details of the cell cycle vary. Embryonic cells in many organisms run a cycle that is shorter than similar cells in the adult. Cells of yeast and mammal show differences in cycle detail but the general mechanism of the cell cycle has been highly conserved over the years. During the cell cycle cytoplasmic chemistry influences to a large extent the activities of the whole cell. At all other times we think in terms of the cell nucleus determining cytoplasmic activity.
The cell cycle system of a eukaryotic organism includes:
A cell is ‘cycled’ through each phase and from phase to phase by the action of proteins including specific cyclins and cyclin dependent kinases (cdks). Different cyclins and cdks rise and fall in activity during the cell cycle. Sometimes faults go undetected (as in industry). Quality control and assurance systems can also fail. Quality control system failure is associated with cell and organ disease and probably as many as 50% of cancers (but this does not mean one single system failure alone will cause cancer). Late G1 phase The main drivers of progression through the cell cycle are called protein kinases. There are several of these and each is a combination of a cyclin and a catalytic enzyme called a cyclin dependent kinase (cdk). The different combinations operate in specific parts of the cell cycle and rise and fall in activity during the cycle. In so doing they contribute to the mechanism of phase entry and exit. The raised level of activity of the various cyclin and cdk combinations is terminated by proteolysis of cyclins after polyubiquitination. (Ubiquitins are a group of proteins that are covalently linked to proteins targeted for degradation. After molecular binding the target proteins, in this case cyclins, are degraded by proteolysis – protein loosening from Greek lusis, ‘loosening’) The first cyclin combination (cyclin D and cdk 4 and 6) trips in about three quarters of the way through G1 phase to be joined later by the cyclin E and cdk 2 combination, both cyclins driving the cell into S phase At about this time the cell passes through the ‘Restriction Point’ (in yeasts called START). This is a point of ‘no return’, the cell cycle equivalent of ‘Caesar crossing the Rubicon’. Once the cell passes this point it is restricted, there is no going back; the cell is committed to replicate in ‘S’ phase. Checkpoints in the cell cycle are not unlike those found at some border crossings where passports, papers and merchandise are checked. At the molecular level a cell cycle checkpoint consists of (1) sensor/detector (2) a signal sender and (3) a receiver/effector. G1 checkpoint The division cycle of a cell with badly damaged DNA may end at this checkpoint. Unfortunately, quality control in cells is not perfect. Very occasionally DNA damage is missed by QC and slightly changed DNA slips through the system. Sometimes this is because the damaged DNA does not trigger the checkpoint system. The quality control system may also be damaged itself. DNA of the p53 gene can be damaged by sunlight (u.v. radiation) and mutagenic chemicals including those from cigarette smoke and aflatoxin from, for example, mouldy peanuts. At the G1 checkpoint in yeast cell cycle, a check is made to ensure cell size is correct for division, but cell size has been found not to be so critical a factor in some cells of higher eukaryotes S (DNA synthesis) phase S phase occupies about a third of total cell cycle time. It is here that under the ‘licensing’ system only one new copy of the cell’s DNA is synthesized. This includes acceptable alterations but also questionable ones not detected by QC because of system errors and breakdown. The failure of the ‘guardian of the genome’ p53 gene to operate due to damage within its own DNA is an example of this. In S phase the double-stranded DNA unwinds into two component strands that serve as templates for the synthesis of a new strand on each. Newly formed units of the bases adenine (A), thymine (T), guanine (G) and cytsosine (C) are attached to compliment bases on the unwound DNA. One set of DNA is now produced for each of the two daughter cells. The process of DNA synthesis consumes a considerable amount of energy. (For details of this process see the textbooks listed on our website for example: Pollard, T. D. & Earnshaw, W. C., ‘Cell Biology’ 1st Edit. 2002. 2nd printing, with additions 2004. Publ: W. B. Saunders). S phase checkpoints There appear to be three types of checkpoint in S phase. Not surprisingly all respond in some way to problems with DNA replication. These problems range from a shortage of deoxyribonucleotides for making new DNA, to the presence of enzyme inhibitory chemicals and breaks in the DNA molecule. The cell cycle can arrest here if the DNA is unreplicated or in any way incomplete and not competent to proceed to phase G2. If everything goes smoothly by the end of S phase the cell will contain two identical sets of its genome. The cycle is driven through S phase and into G2 phase by the cyclin A and cdk 2 combination. G2 (Gap 2) phase G2 Checkpoint At the G2 checkpoint:
M phase (mitosis) Cyclin A and B coupled to cdk 1 drives the cell through mitosis (the student is referred to a textbook at the desired level for detailed information about mitosis). At the end of mitosis the sister chromatids, joined as pairs by cohesive ‘glue’ since they were replicated in S phase, are separated to form two new equivalent sets of chromosomes. This event is chromosome segregation. Some organelles in the cytoplasm are disassembled into molecular units to be divided during division of the cytoplasm (kinesis), and then new ones constructed in the daughter cells. Other cytoplasmic inclusions are shared (not always evenly) between the daughter cells. M phase (mitosis) checkpoints The working of one checkpoint within mitosis, the metaphase checkpoint, is well established. There may be more checkpoints but further work is needed to establish their existence. Metaphase checkpoint Also called ‘spindle assembly or kinetochore attachment checkpoint’ it operates during metaphase and before the cell enters anaphase. It checks for misaligned chromosomes and also that microtubules are attached to kinetochores – a very critical mechanism. The start of anaphase is delayed until all the chromosomes are aligned and appropriately attached. When telophase is complete cytokinesis – (the division of cytoplasm) takes place. After this the two daughter cells will be directed to G-0 (zero) or G1 phase. CONCEPT MESSAGES:
CHALLENGE YOUR CRITICAL THINKING:
SELECTED WEBSITES: http://www.cancerresearchuk.org http://www.cellsalive.com Grateful thanks are due to Margarete Heck for her valuable contribution. Diagram ‘Cell cycle control in mammalian cultured cells’
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