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ScienceWeek
CELL BIOLOGY: ON THE PROKARYOTIC CELL CYCLE
The following points are made by W. Margolin and R. Bernander (Current Biology 2004 14:R768):
1) Until recently, it appeared that prokaryotes and eukaryotes, with their different levels of complexity and cellular structure, did not share much kinship in cell-cycle mechanics. But with the rapid increase in the number of complete prokaryotic genome sequences, and advances in prokaryotic cell biology, surprising similarities have emerged that for some organisms suggest a direct evolutionary connection. Additional evidence indicates that in other prokaryotes the cell cycle is fundamentally different from the eukaryotic paradigm.
2) The initiation of chromosomal DNA replication in eukaryotes is characterized by the use of multiple replication origins, followed by the prevention of reinitiation until the next cell cycle. Origin recognition complex (ORC) proteins recognize the origins and direct the replication machinery to the correct locations in the chromosomes, thereby providing specificity to the process, and also directly participate in replication initiation. The archaea have a set of DNA replication proteins that is entirely homologous to that of eukaryotes, including one, or several, CDC6/ORC1-like proteins. Furthermore, several archaeal species have recently been shown to initiate replication in synchrony from multiple origins, providing yet another fundamental similarity to eukaryotes.
3) Key aspects of replication have thus been evolutionarily conserved across two kingdoms, and further study of the archaea will reveal to what extent cell-cycle control mechanisms also may be conserved. In the other major branch of prokaryotic life, the bacteria, the DnaA replication initiator protein is also structurally and functionally related to CDC6/ORC1, although more distantly, and ORC1 and DnaA also share the property of being involved in the transcriptional regulation of other genes. But in all bacterial species analyzed to date, chromosome replication is initiated at a single origin (oriC).
4) In eukaryotes, the reinitiation of replication is prevented by tight cell-cycle control over origin firing. This regulation requires a two-step system involving cyclin-dependent kinases (CDKs), which are regulated by cell-cycle dependent oscillation of cyclin levels, and the anaphase promoting complex/cyclosome (APC/C). High CDK activity prevents formation of the replication complex during S, G2, and M phases, and licensing of replication is renewed only in G1, prior to the next S phase. In archaea from the genus Sulfolobus, Orc1/Cdc6 protein levels vary dramatically over the cell cycle, similar to the variation in cyclin abundance over the eukaryotic cell cycle, although no cyclin homologues have yet been identified.
5) Bacteria such as Escherichia coli also prevent reinitiation at oriC until the next cell cycle, but their strategy is very different from that of eukaryotes. Instead of using a dedicated cell-cycle control system for replicative licensing, both the DnaA initiator and the oriC chromosome region are made transiently inactive in E. coli after initiation starts. This period of inactivity lasts a significant fraction of the cell cycle, thus accomplishing the same goals as in eukaryotes.
Current Biology http://www.current-biology.com
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THEORETICAL BIOLOGY: CONTROLLING CELL CYCLE DYNAMICS
Notes by ScienceWeek:
During the past few decades, studies of the *cell division cycle have revealed many of the genes and proteins that drive and regulate cell division, and methods for the artificial control of the cell cycle have become apparent. Such manipulations are typically achieved by introducing mutations into the genes that regulate the cycle. These mutations, however, usually result in uncontrolled cell division, or complete suppression of cell division, or cause the cell to commit fatal errors during the cell cycle.
The following points are made by T.S. Gardner et al (Proc. Nat. Acad. Sci. 1998 95:14190):
1) Using mathematical modeling of cell division cycle dynamics, the authors report a potential mechanism for the precise control of the frequency of cell division and regulation of the size of the dividing cell. The work of the authors involves the application of a specific biochemical constraint to two already existing mathematical models of cell cycle dynamics (models by A. Goldbeter; B. Novak and J.J. Tyson). The authors report that control of the cell cycle in their application is achieved by artificially expressing a protein that reversibly binds and inactivates any one of the cell division cycle proteins.
2) In the simplest case (the Goldbeter model), the frequency of cell division cycle oscillations can be increased or decreased by regulating the rate of synthesis, the binding rate, or the equilibrium constant of the binding protein. In a more complex model of cell division (the Novak-Tyson model), the authors report that the same reversible binding reaction can alter the mean cell mass in a continuously dividing cell.
3) The authors suggest that because their control scheme is general and requires only the expression of a single protein, it provides a practical means for tuning the characteristics of the cell cycle in vivo.
Proc. Nat. Acad. Sci. http://www.pnas.org
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Notes by ScienceWeek:
cell division cycle: (cell cycle) Prior to each cell division, a cell passes through a series of preparatory stages that are collectively known as the "cell cycle". The cycle is considered to begin when two new cells are formed by the division of a single parent cell, and it ends when one of these new cells in turn divides to form two more cells. The paramount process is the transfer of a complete set of genetic instructions to each new cell. The periodicity of the cycle varies from one type of cell to another, and within a single type, the periodicity can also vary in response to ambient conditions. Laboratory methods are now available to not only control the periodicity of the cell cycle, but also to synchronize the periodicities of a population of cultured cells. The obvious oscillatory behavior of biological cells has for many decades been the focus of much research involving mathematical modeling.
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CELL BIOLOGY: ON MITOSIS
The following points are made by C.L. Rieder and A. Khodjakov (Science 2003 300:91):
1) The German anatomist Walther Flemming (1843-1905) was one of the first to describe the cell division process. In 1882 he coined the term "mitosis" to characterize the formation of paired threads (Greek = mitos) during division of the cell nucleus. These threads, which formed from a substance Flemming called "chromatin", came to be known as the "chromosomes". The definition of mitosis has since been expanded to include "cytokinesis", the process by which the cell cytoplasm is partitioned at the end of nuclear division.
2) Until the late 1940s, research on mitosis was primarily restricted to an examination of cells that had been preserved in a lifelike state by chemicals (the condition called "fixed") and then colored with dyes to generate contrast between their different components. These descriptions revealed that the division process is fundamentally the same in all somatic cells.
3) In animals, mitosis is mediated by a bipolar spindle-shaped apparatus that appears to be assembled in the cytoplasm from two radial arrays of fibers, known as "asters". These asters form in association with two separating "centrosomes" that define the spindle poles. Early studies also noted that each chromosome possesses two small organelles on its surface that are positioned back-to-back and on opposite sides of the chromosome. As the spindle forms, these "kinetochores" acquire fibers that attach them to one of the spindle poles, so that opposing sister kinetochores are attached to opposite poles. Collectively, the spindle and its associated centrosomes, kinetochores, and chromosomes are referred to as the "mitotic apparatus".
4) Flemming noted that the chromosomes, which are scattered throughout the cytoplasm after nuclear envelope breakdown, are collected by the spindle and positioned on a plane halfway between the two poles. After this "metaphase" alignment is completed, the two chromatids forming each chromosome disjoin, and each moves toward its respective pole in a process termed "anaphase". Once the two groups of chromosomes reach their respective poles, they coalesce to form the new daughter nuclei, after which cytokinesis pinches the cytoplasm into two new cells.
Science http://www.sciencemag.org
ScienceWeek http://scienceweek.com
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