Biorientation

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Biorientation is the phenomenon whereby microtubules emanating from different microtubule organizing centres (MTOCs) attach to kinetochores of sister chromatids. This results in the sister chromatids moving to opposite poles of the cell during cell division, and thus results in both daughter cells having the same genetic information.

Kinetochores link the chromosomes to the mitotic spindle - doing so relies on intricate interactions between microtubules and kinetochores. [1] It has been shown that, in fission yeast, microtubule attachment can make frequent erroneous attachments early in mitosis, which are then often corrected prior to anaphase onset by a system which uses protein kinase to affect kinetochore microtubules (ktMTs) in the absence of astriction between sister chromatids. [2]

Proper biorientation allows correct chromosomal segregation in cell division. [3] Although this process is not well understood, high-resolution imaging of live mouse oocytes has revealed that chromosomes form an intermediate chromosomal configuration, called the prometaphase belt, which occurs prior to biorientation. Kitajima, et al. estimate that about 90% of chromosomes require correction of the kinetochore-microtubule attachments (using Aurora kinase )prior to obtaining correct biorientation. [3] This suggests a possible cause for the elevated frequency of abnormal chromosome counts (aneuploidy) in mammals. [3]

Several methods are postulated by which chromosomes biorient when they are located far from the pole with which they need to connect. One mechanism involves the kinetchore meeting microtubules from the distal pole. Another method described is based on observations that the kinetochore of one pole-oriented chromosome attaches to kinetochore fibers of an already bioriented chromosome. These two mechanisms possibly work in concert - certain chromosomes may biorient via encounters with microtubules from distal poles, which is then followed by kinetochore fibers that speed up biorientation with already-oriented chromosomes. [4] Researchers have detached grasshopper spermatocytes from spindle fibers and moved them away from the metaphase plate via micromanipulation. Several chromosomes instantly bioriented, as deduced from the observation that, upon reattachment, the chromosomes moved to the metaphase plate without moving to the poles. [4]

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Meiosis Type of cell division in sexually-reproducing organisms used to produce gametes

Meiosis is a special type of cell division of germ cells in sexually-reproducing organisms used to produce the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately result in four cells with only one copy of each chromosome (haploid). Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is crossed over, creating new combinations of code on each chromosome. Later on, during fertilisation, the haploid cells produced by meiosis from a male and female will fuse to create a cell with two copies of each chromosome again, the zygote.

Mitosis The division of a cell nucleus in which the genome is copied and separated into two identical halves

In cell biology, 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. Therefore, mitosis is also known as equational division. In general, mitosis is preceded by the S stage of interphase and is often 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 altogether define the mitotic (M) phase of an animal cell cycle—the division of the mother cell into two daughter cells genetically identical to each other.

Cell division The process resulting in division and partitioning of components of a cell to form more cells; may or may not be accompanied by the physical separation of a cell into distinct, individually membrane-bounded daughter cells.

Cell division is the process by which a parent cell divides into two or more daughter cells. Cell division usually occurs as part of a larger cell cycle. In eukaryotes, there are two distinct types of cell division; a vegetative division, whereby each daughter cell is genetically identical to the parent cell (mitosis), and a reproductive cell division, whereby the number of chromosomes in the daughter cells is reduced by half to produce haploid gametes (meiosis). In cell biology, mitosis (/maɪˈtoʊsɪs/) 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 often 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 mitotic (M) phase of an animal cell cycle—the division of the mother cell into two genetically identical daughter cells. Meiosis results in four haploid daughter cells by undergoing one round of DNA replication followed by two divisions. Homologous chromosomes are separated in the first division, and sister chromatids are separated in the second division. 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.

Anaphase Stage of a cell division

Anaphase, is the stage of mitosis after the process of metaphase, when replicated chromosomes are split and the newly-copied chromosomes are moved to opposite poles of the cell. Chromosomes also reach their overall maximum condensation in late anaphase, to help chromosome segregation and the re-formation of the nucleus.

Spindle apparatus Array of microtubules and associated molecules that forms between opposite poles of a eukaryotic cell during mitosis or meiosis and serves to move the duplicated chromosomes apart

In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.

Telophase Final stage of a cell division for eukaryotic cells both in mitosis and meiosis

Telophase is the final stage in both meiosis and mitosis in a eukaryotic cell. During telophase, the effects of prophase and prometaphase are reversed. As chromosomes reach the cell poles, a nuclear envelope is re-assembled around each set of chromatids, the nucleoli reappear, and chromosomes begin to decondense back into the expanded chromatin that is present during interphase. The mitotic spindle is disassembled and remaining spindle microtubules are depolymerized. Telophase accounts for approximately 2% of the cell cycle's duration.

Cyclin

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.

Spindle checkpoint

The spindle checkpoint, also known as the metaphase-to-anaphase transition, the spindle assembly checkpoint (SAC), or the mitotic checkpoint, is a cell cycle checkpoint during mitosis or meiosis that prevents the separation of the duplicated chromosomes (anaphase) until each chromosome is properly attached to the spindle. To achieve proper segregation, the two kinetochores on the sister chromatids must be attached to opposite spindle poles. Only this pattern of attachment will ensure that each daughter cell receives one copy of the chromosome. The defining biochemical feature of this checkpoint is the stimulation of the anaphase-promoting complex by M-phase cyclin-CDK complexes, which in turn causes the proteolytic destruction of cyclins and proteins that hold the sister chromatids together.

Kinetochore Protein complex that allows microtubules to attach to chromosomes during cell division

A kinetochore is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis. Its proteins also help to hold the sister chromatids together and play a role in chromosome editing. Details of the specific areas of origin are unknown.

Mad2 is an essential spindle checkpoint protein. The spindle checkpoint system is a regulatory system that restrains progression through the metaphase-to-anaphase transition. The Mad2 gene was first identified in the yeast S. cerevisiae in a screen for genes which when mutated would confer sensitivity to microtubule poisons. The human orthologues of Mad2 were first cloned in a search for human cDNAs that would rescue the microtubule poison-sensitivity of a yeast strain in which a kinetochore binding protein was missing. The protein was shown to be present at unattached kinetochores and antibody inhibition studies demonstrated it was essential to execute a block in the metaphase-to-anaphase transition in response to the microtubule poison nocodazole. Subsequent cloning of the Xenopus laevis orthologue, facilitated by the sharing of the human sequence, allowed for the characterization of the mitotic checkpoint in egg extracts.

Aurora A kinase

Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the AURKA gene.

Aurora B kinase Protein

Aurora B kinase is a protein that functions in the attachment of the mitotic spindle to the centromere.

Anaphase lag is a consequence of an event during cell division where sister chromatids do not properly separate from each other because of improper spindle formation. The chromosome or chromatid does not properly migrate during anaphase and the daughter cells will lose some genetic information. It is one of many causes of aneuploidy. This event can occur during both meiosis and mitosis with unique repercussions. In either case, anaphase lag will cause one daughter cell to receive a complete set of chromosomes while the other lacks one paired set of chromosomes, creating a form of monosomy. Whether the cell survives depends on which sister chromatid was lost and the background genomic state of the cell. The passage of abnormal numbers of chromosomes will have unique consequences with regards to mosaicism and development as well as the progression and heterogeneity of cancers.

Polo-like kinases (Plks) are regulatory serine/threonin kinases of the cell cycle involved in mitotic entry, mitotic exit, spindle formation, cytokinesis, and meiosis. Only one Plk is found in the genomes of fruit flies (Polo), budding yeast (Cdc5) and fission yeast (Plo1). Vertebrates, however, have many Plk family members including Plk1, Plk2/Snk, Plk3/Prk/FnK, Plk4/Sak and Plk5. Of the vertebrate Plk family members, the mammalian Plk1 has been most extensively studied. During mitosis and cytokinesis, Plks associate with several structures including the centrosome, kinetochores, and the central spindle.

BUB1

Mitotic checkpoint serine/threonine-protein kinase BUB1 also known as BUB1 is an enzyme that in humans is encoded by the BUB1 gene.

BUB3

Mitotic checkpoint protein BUB3 is a protein that in humans is encoded by the BUB3 gene.

Syntelic attachment occurs when both sister chromosomes are attached to a single spindle pole.

Mad1

Mad1 is a non-essential protein which in yeast has a function in the spindle assembly checkpoint (SAC). This checkpoint monitors chromosome attachment to spindle microtubules and prevents cells from starting anaphase until the spindle is built up. The name Mad refers to the observation that mutant cells are mitotic arrest deficient (MAD) during microtubule depolymerization. Mad1 recruits the anaphase inhibitor Mad2 to unattached kinetochores and is essential for Mad2-Cdc20 complex formation in vivo but not in vitro. In vivo, Mad1 acts as a competitive inhibitor of the Mad2-Cdc20 complex. Mad1 is phosphorylated by Mps1 which then leads together with other activities to the formation of the mitotic checkpoint complex (MCC). Thereby it inhibits the activity of the anaphase-promoting complex/cyclosome (APC/C). Homologs of Mad1 are conserved in eukaryotes from yeast to mammals.

In molecular biology, the protein domain named the Shugoshin N-terminal coiled-coil region is a domain found on the N-terminal region of the Shugoshin protein in eukaryotes. It has a role in attaching to the kinetochores, structures on the chromatids where microtubules attach. Shugoshin has a conserved coiled-coil N-terminal domain and a highly conserved C-terminal region. Shugoshin is a crucial target of Bub1 kinase that plays a central role in the cohesion of chromosomes during cell division.

The XMAP215/Dis1 family is a highly conserved group of microtubule-associated proteins (MAPs) in eukaryotic organisms. These proteins are unique MAPs because they primarily interact with the growing-end (plus-end) of microtubules. This special property classifies this protein family as plus-end tracking proteins (+TIPs).

References

  1. C.B. O'Connell; A. Khodjakov & B.F. McEwen (2012). "Kinetochore flexibility: creating a dynamic chromosome-spindle interface". Current Opinion in Cell Biology. 24: 40–47. doi:10.1016/j.ceb.2011.12.008. PMC   3507511 . PMID   22221609.
  2. G. Gay; T. Courtheoux; C. reyes; S. Tournier & B.F. McEwen (2012). "A stochastic model of kinetochore-microtubule attachment accurately describes fission yeast chromosome segregation". Journal of Cell Biology. 196: 757–774. doi:10.1083/jcb.201107124. PMC   3308688 . PMID   22412019.
  3. 1 2 3 T.S. Kitajima; M. Ohsugi & J. Ellenberg (2011). "Complete kinetochore tracking reveals error-prone homologous chromosome biorientation in mammalian oocytes". Cell. 146: 568–581. doi: 10.1016/j.cell.2011.07.031 . PMID   21854982.
  4. 1 2 J.R. Geert; L. Kops; A.T. Saurin & P. Meraldi (2010). "Fiinding the middle ground: how kinetochores power chromosome congression". Cellular and Molecular Life Sciences. 67: 2145–2161. doi:10.1007/s00018-010-0321-y. PMC   2883098 . PMID   20232224.