Mitosis onset

APC is active from mid-M phase (anaphase) to the end of G1 phase and required for disconnecting sister chromatids and exit from M-Phase to Gl. The complex mediates the ubiquitination of Securin and Cyclin B. Degradation of these proteins, which block mitotic progression, promotes anaphase onset and exit from mitosis. 

Abstract. In eukaryotic cells, replicated DNA molecules remain physically connected from their synthesis in S phase until they are separated during anaphase. This phenomenon, called sister chromatid cohesion, is essential for the temporal separation of DNA replication and mitosis and for the equal separation of the duplicated genome. Recent work has identified a number of chromosomal proteins required for cohesion. In this review we discuss how these proteins may connect sister chromatids and how they are removed from chromosomes to allow sister chromatid separation at the onset of anaphase. 

Histone HI can be modified through phosphorylation (Langan and Hohmann, 1975). A change in the extent of HI phosphorylation was correlated with the onset of mitosis (Lake and Salzman, 1972) and it has been suggested that this serves as a trigger for chromosome con-... 

To determine the effect of circadian rhythms on anticancer drug administration, it is important to incorporate the link between the circadian clock and the cell cycle. Entrainment by the circadian clock can be included in the automaton model by considering that the protein Weel undergoes circadian variation, because the circadian clock proteins CLOCK and BMAL1 induce the expression of the Weel gene (see Fig. 10.1b) [3-5]. Weel is a kinase that phosphorylates and thereby inactivates the protein kinase cdc2 (also known as the cyclin-dependent kinase Cdkl) that controls the transition G2/M and, consequently, the onset of mitosis. 

A 34 kDa protein (p34) plays an important function in the control of the cell cycle in all eukaryotes. It was first identified as the product of the cdc 2/cdc 28 gene in yeast mutants which caused cells to be arrested at a commitment point in G1 (Murray, 1981). However, anti-p34 antibodies injected into cells do not affect DNA synthesis but block cells in mitosis (Riabowol et al., 1989) and p34 is believed to function both at the onset of S-phase and at mitosis. 

The polyamines putrescine, spermidine, and spermine have been identified in Jerusalem artichoke tubers (Serafini-Fracassini et al., 1980), though Phillips et al. (1987) found spermidine, diaminopropane, and cadaverine during the initial 24-h activation and onset of mitosis. Both research groups found a correlation between polyamine levels and early cell division, and that polyamines could induce a limited pattern of cell division. 

It is clear from observing chromosome movements that cell division occurs in an ordered sequence of events (Fig. la). First chromosomes attach to spindle microtubule fibers and move to the spindle equator. Only after completion of this step do sister chromosomes separate at anaphase and move to opposite sides of the cell, followed by their division into two daughter cells. Events must occur in this order for successful chromosome segregation. If the cell enters anaphase prematurely, before chromosomes have attached properly to the spindle, the sister chromosomes will not segregate equally, which leads to aneu-ploid daughter cells. Therefore, mechanisms that determine the timing of anaphase onset are critical for the success of mitosis. 

At the cellular level, bursts of HA synthesis correlate with the onset of mitosis [34,35,63]. This disengages the cell from the ECM and tissue organization, and prepares the cell for the semi-autonomous situation required for cell division. At the completion of mitosis, or at the beginning of Go phase of the cell cycle, a burst of hyaluronidase expression may occur, removing the shell of pericellular HA, preparing the cell for re-association with the ECM... 

Levels of HA deposition respond to the various physiological states of the cell. In cultures of normal animal cells, growth phase [34], and degrees of confluence are inversely related to HA levels in both fibroblasts [106] and keratinocytes [38]. HA has been correlated with the onset of mitosis and detachment from the substratum [35], calcium concentrations [107], anoxia and lactate levels [108], viral transformation [109], and serum stimulation [110,111]. 

Extracts of whole ripe and unripe berries, seed, pulp, root, leaf, and stem produce erythrocyte agglutination and leukocyte mitosis (Fames et al., 1964). A glycoprotein known as pokeweed mitogen is responsible for leukocyte mitosis, and in pokeweed poisonings, plasmacytosis variable in onset and lasting 2 mo or longer is seen (Barker et al., 1966 Roberge et al., 1986). 

Microtubule dynamics change drastically at the onset of mitosis, when long interphase microtubules disappear and are replaced by astral and spindle microtubules. These mitotic microtubules, which are nucleated from the newly duplicated centrosomes, are more numerous, shorter, and less stable than interphase microtubules. The average lifetime of a microtubule decreases from 10 minutes In Interphase cells to 60-90 seconds in the mitotic apparatus. This Increase In dynamic instability enables microtubules to assemble and disassemble quickly in mitosis. 

Further studies revealed that vertebrate cells contain three proteins that can function like cyclin B to stimulate Xenopus oocyte maturation two closely related cyclin Bs and cyclin A. Collectively called B-type cyclins, these proteins exhibit regions of high sequence homology. (B-type cyclins are distinguished from Gi cyclins described in Section 21.5.) In intact cells, degradation of all the B-type cyclins begins after the onset of anaphase, the period of mitosis when sister chromatids are separated and pulled toward opposite spindle poles. 

MPF is a protein kinase that requires a mitotic cyciin for activity. The protein kinase activity of MPF stimulates the onset of mitosis by phosphorylatlng multiple specific protein substrates, most of which remain to be identified. 

A decrease in Weel activity and increase in Cdc25 activity, resulting in activation of the mitotic cyclin-CDK complex, results in the onset of mitosis. 

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