Meiomitosis

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In cell biology, Meiomitosis is an aberrant cellular division pathway that combines normal mitosis pathways with ectopically expressed meiotic machinery resulting in genomic instability. [1]

Contents

Description

Meiotic pathways are normally restricted to germ cells. Meiotic proteins drive double stranded DNA breaks, chiasma formation, sister chromatid adhesion and rearrange the spindle apparatus. [2]  

During meiosis, there are 2 sets of cell divisions, the second division is similar to mitosis in that sister chromatids are directly separated.  However, in the first meiotic division the sister chromatids are held together by cohesins and segregated from their homologous pair of cohesion bound sister chromatids after resolution of recombination crossover points (chiasma) between the homologous pairs.  The collision of mitosis and meiosis (first division) pathways could cause abnormal chiasma formation, abnormal cohesion expression, and mitotic/meiotic spindle defects that could result in insertions, deletions, abnormal segregation, DNA bridging, and potentially failure of cell division altogether resulting in polyploidy.

Role in cancer

Meiotic proteins have been noted to be expressed in cancer particularly melanoma [3] and lymphoma. In cutaneous T-cell lymphoma meiosis proteins have been shown to be regulated with the cell cycle. [4]   Lymphoma cell lines have also been noted to up-regulate meiosis specific genes with irradiation and a correlation with mitotic arrest and polyploidy has been noted. [5]  The overall role of meiomitosis in cancer development and evolution has yet to be determined.

Related Research Articles

<span class="mw-page-title-main">Meiosis</span> Cell division producing haploid gametes

Meiosis is a special type of cell division of germ cells in sexually-reproducing organisms that produces 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 a female will fuse to create a cell with two copies of each chromosome again, the zygote.

<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 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 animal cell cycle—the division of the mother cell into two genetically identical daughter cells. 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.

<span class="mw-page-title-main">Chromosomal crossover</span> Cellular process

Chromosomal crossover, or crossing over, is the exchange of genetic material during sexual reproduction between two homologous chromosomes' non-sister chromatids that results in recombinant chromosomes. It is one of the final phases of genetic recombination, which occurs in the pachytene stage of prophase I of meiosis during a process called synapsis. Synapsis begins before the synaptonemal complex develops and is not completed until near the end of prophase I. Crossover usually occurs when matching regions on matching chromosomes break and then reconnect to the other chromosome.

<span class="mw-page-title-main">Prophase</span> First phase of cell division in both mitosis and meiosis

Prophase is the first stage of cell division in both mitosis and meiosis. Beginning after interphase, DNA has already been replicated when the cell enters prophase. The main occurrences in prophase are the condensation of the chromatin reticulum and the disappearance of the nucleolus.

<span class="mw-page-title-main">Nondisjunction</span> Failure to separate properly during cell division

Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division (mitosis/meiosis). There are three forms of nondisjunction: failure of a pair of homologous chromosomes to separate in meiosis I, failure of sister chromatids to separate during meiosis II, and failure of sister chromatids to separate during mitosis. Nondisjunction results in daughter cells with abnormal chromosome numbers (aneuploidy).

Maturation-promoting factor (abbreviated MPF, also called mitosis-promoting factor or M-Phase-promoting factor) is the cyclin-Cdk complex that was discovered first in frog eggs. It stimulates the mitotic and meiotic phases of the cell cycle. MPF promotes the entrance into mitosis (the M phase) from the G2 phase by phosphorylating multiple proteins needed during mitosis. MPF is activated at the end of G2 by a phosphatase, which removes an inhibitory phosphate group added earlier.

<span class="mw-page-title-main">Spindle checkpoint</span> Cell cycle checkpoint

The spindle checkpoint, also known as the metaphase-to-anaphase transition, the spindle assembly checkpoint (SAC), the metaphase checkpoint, or the mitotic checkpoint, is a cell cycle checkpoint during metaphase of 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.

<span class="mw-page-title-main">Kinetochore</span> 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. The term kinetochore was first used in a footnote in a 1934 Cytology book by Lester W. Sharp and commonly accepted in 1936. Sharp's footnote reads: "The convenient term kinetochore has been suggested to the author by J. A. Moore", likely referring to John Alexander Moore who had joined Columbia University as a freshman in 1932.

<span class="mw-page-title-main">Heteroduplex</span>

A heteroduplex is a double-stranded (duplex) molecule of nucleic acid originated through the genetic recombination of single complementary strands derived from different sources, such as from different homologous chromosomes or even from different organisms.

<span class="mw-page-title-main">Synapsis</span> Biological phenomenon in meiosis

Synapsis is the pairing of two chromosomes that occurs during meiosis. It allows matching-up of homologous pairs prior to their segregation, and possible chromosomal crossover between them. Synapsis takes place during prophase I of meiosis. When homologous chromosomes synapse, their ends are first attached to the nuclear envelope. These end-membrane complexes then migrate, assisted by the extranuclear cytoskeleton, until matching ends have been paired. Then the intervening regions of the chromosome are brought together, and may be connected by a protein-RNA complex called the synaptonemal complex. During synapsis, autosomes are held together by the synaptonemal complex along their whole length, whereas for sex chromosomes, this only takes place at one end of each chromosome.

<span class="mw-page-title-main">Sister chromatids</span> Two identical copies of a chromosome joined at the centromere

A sister chromatid refers to the identical copies (chromatids) formed by the DNA replication of a chromosome, with both copies joined together by a common centromere. In other words, a sister chromatid may also be said to be 'one-half' of the duplicated chromosome. A pair of sister chromatids is called a dyad. A full set of sister chromatids is created during the synthesis (S) phase of interphase, when all the chromosomes in a cell are replicated. The two sister chromatids are separated from each other into two different cells during mitosis or during the second division of meiosis.

<span class="mw-page-title-main">Bivalent (genetics)</span>

A bivalent is one pair of chromosomes in a tetrad. A tetrad is the association of a pair of homologous chromosomes physically held together by at least one DNA crossover. This physical attachment allows for alignment and segregation of the homologous chromosomes in the first meiotic division. In most organisms, each replicated chromosome elicits formation of DNA double-strand breaks during the leptotene phase. These breaks are repaired by homologous recombination, that uses the homologous chromosome as a template for repair. The search for the homologous target, helped by numerous proteins collectively referred as the synaptonemal complex, cause the two homologs to pair, between the leptotene and the pachytene phases of meiosis I.

Chromosome segregation is the process in eukaryotes by which two sister chromatids formed as a consequence of DNA replication, or paired homologous chromosomes, separate from each other and migrate to opposite poles of the nucleus. This segregation process occurs during both mitosis and meiosis. Chromosome segregation also occurs in prokaryotes. However, in contrast to eukaryotic chromosome segregation, replication and segregation are not temporally separated. Instead segregation occurs progressively following replication.

<span class="mw-page-title-main">PLK1</span> Mammalian protein found in Homo sapiens

Serine/threonine-protein kinase PLK1, also known as polo-like kinase 1 (PLK-1) or serine/threonine-protein kinase 13 (STPK13), is an enzyme that in humans is encoded by the PLK1 gene.

<span class="mw-page-title-main">TRIP13</span> Protein-coding gene in the species Homo sapiens

TRIP13 is a mammalian gene that encodes the thyroid receptor-interacting protein 13. In budding yeast, the analog for TRIP13 is PCH2. TRIP13 is a member of the AAA+ ATPase family, a family known for mechanical forces derived from ATP hydrolase reactions. The TRIP13 gene has been shown to interact with a variety of proteins and implicated in a few diseases, notably interacting with the ligand binding domain of thyroid hormone receptors, and may play a role in early-stage non-small cell lung cancer. However, recent evidence implicates TRIP13 in various cell cycle phases, including meiosis G2/Prophase and during the Spindle Assembly checkpoint (SAC). Evidence shows regulation to occur through the HORMA domains, including Hop1, Rev7, and Mad2. Of note, Mad2's involvement in the SAC is shown to be affected by TRIP13 Due to TRIP13's role in cell cycle arrest and progression, it may present opportunity as a therapeutic candidate for cancers.

<span class="mw-page-title-main">Chiasma (genetics)</span>

In genetics, a chiasma is the point of contact, the physical link, between two (non-sister) chromatids belonging to homologous chromosomes. At a given chiasma, an exchange of genetic material can occur between both chromatids, what is called a chromosomal crossover, but this is much more frequent during meiosis than mitosis. In meiosis, absence of a chiasma generally results in improper chromosomal segregation and aneuploidy.

<span class="mw-page-title-main">Mitotic catastrophe</span>

Mitotic catastrophe has been defined as either a cellular mechanism to prevent potentially cancerous cells from proliferating or as a mode of cellular death that occurs following improper cell cycle progression or entrance. Mitotic catastrophe can be induced by prolonged activation of the spindle assembly checkpoint, errors in mitosis, or DNA damage and functioned to prevent genomic instability. It is a mechanism that is being researched as a potential therapeutic target in cancers, and numerous approved therapeutics induce mitotic catastrophe.

Sister chromatid cohesion refers to the process by which sister chromatids are paired and held together during certain phases of the cell cycle. Establishment of sister chromatid cohesion is the process by which chromatin-associated cohesin protein becomes competent to physically bind together the sister chromatids. In general, cohesion is established during S phase as DNA is replicated, and is lost when chromosomes segregate during mitosis and meiosis. Some studies have suggested that cohesion aids in aligning the kinetochores during mitosis by forcing the kinetochores to face opposite cell poles.

<span class="mw-page-title-main">SMC1B</span> Protein-coding gene in the species Homo sapiens

Structural maintenance of chromosomes protein 1B (SMC-1B) is a protein that in humans is encoded by the SMC1B gene. SMC proteins engage in chromosome organization and can be broken into 3 groups based on function which are cohesins, condensins, and DNA repair.SMC-1B belongs to a family of proteins required for chromatid cohesion and DNA recombination during meiosis and mitosis. SMC1ß protein appears to participate with other cohesins REC8, STAG3 and SMC3 in sister-chromatid cohesion throughout the whole meiotic process in human oocytes.

Chromosomal instability (CIN) is a type of genomic instability in which chromosomes are unstable, such that either whole chromosomes or parts of chromosomes are duplicated or deleted. More specifically, CIN refers to the increase in rate of addition or loss of entire chromosomes or sections of them. The unequal distribution of DNA to daughter cells upon mitosis results in a failure to maintain euploidy leading to aneuploidy. In other words, the daughter cells do not have the same number of chromosomes as the cell they originated from. Chromosomal instability is the most common form of genetic instability and cause of aneuploidy.

References

  1. Grichnik, James M. (October 2008). "Melanoma, nevogenesis, and stem cell biology". The Journal of Investigative Dermatology. 128 (10): 2365–2380. doi: 10.1038/jid.2008.166 . ISSN   1523-1747. PMID   18787546.
  2. Ross, Andrew L.; Leder, Daniel E.; Weiss, Jonathan; Izakovic, Jan; Grichnik, James M. (September 2011). "Genomic instability in cultured stem cells: associated risks and underlying mechanisms". Regenerative Medicine. 6 (5): 653–662. doi:10.2217/rme.11.44. ISSN   1746-076X. PMID   21916599.
  3. Lindsey, Scott F.; Byrnes, Diana M.; Eller, Mark S.; Rosa, Ashley M.; Dabas, Nitika; Escandon, Julia; Grichnik, James M. (2013). "Potential role of meiosis proteins in melanoma chromosomal instability". Journal of Skin Cancer. 2013: 190109. doi:10.1155/2013/190109. ISSN   2090-2905. PMC   3694528 . PMID   23840955.
  4. Tsang, Matthew; Gantchev, Jennifer; Netchiporouk, Elena; Moreau, Linda; Ghazawi, Feras M.; Glassman, Steven; Sasseville, Denis; Litvinov, Ivan V. (2018-12-28). "A study of meiomitosis and novel pathways of genomic instability in cutaneous T-cell lymphomas (CTCL)". Oncotarget. 9 (102): 37647–37661. doi:10.18632/oncotarget.26479. ISSN   1949-2553. PMC   6340880 . PMID   30701021.
  5. Kalejs, Martins; Ivanov, Andrey; Plakhins, Gregory; Cragg, Mark S.; Emzinsh, Dzintars; Illidge, Timothy M.; Erenpreisa, Jekaterina (2006-01-09). "Upregulation of meiosis-specific genes in lymphoma cell lines following genotoxic insult and induction of mitotic catastrophe". BMC Cancer. 6: 6. doi:10.1186/1471-2407-6-6. ISSN   1471-2407. PMC   1351196 . PMID   16401344.

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