Stages of early mitosis in a vertebrate cell with micrographs of chromatids

Metaphase ( and ) is a stage of

mitosis Mitosis () is a part of the cell cycle in eukaryote, eukaryotic cells in which replicated chromosomes are separated into two new Cell nucleus, nuclei. Cell division by mitosis is an equational division which gives rise to genetically identic ...

in the

eukaryotic The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

cell cycle The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...

in which chromosomes are at their second-most condensed and coiled stage (they are at their most condensed in

anaphase Anaphase () is the stage of mitosis after the process of metaphase, when replicated chromosomes are split and the newly-copied chromosomes (daughter chromatids) are moved to opposite poles of the cell. Chromosomes also reach their overall maxim ...

). These

chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...

s, carrying

genetic information A nucleic acid sequence is a succession of Nucleobase, bases within the nucleotides forming alleles within a DNA (using GACT) or RNA (GACU) molecule. This succession is denoted by a series of a set of five different letters that indicate the orde ...

, align in the equator of the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

between the spindle poles at the metaphase plate, before being separated into each of the two daughter nuclei. This alignment marks the beginning of metaphase. Metaphase accounts for approximately 4% of the

's duration. In metaphase, microtubules from both duplicated

centrosome In cell biology, the centrosome (Latin centrum 'center' + Greek sōma 'body') (archaically cytocentre) is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle progre ...

s on opposite poles of the cell have completed attachment to

kinetochore A kinetochore (, ) is a flared oblique-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers, which can be thought of as the ropes pulling chromosomes apart, attach during cell division to ...

s on condensed chromosomes. The

centromere The centromere links a pair of sister chromatids together during cell division. This constricted region of chromosome connects the sister chromatids, creating a short arm (p) and a long arm (q) on the chromatids. During mitosis, spindle fiber ...

s of the chromosomes convene themselves on the metaphase plate, an imaginary line that is equidistant from the two spindle poles. This even alignment is due to the counterbalance of the pulling powers generated by the opposing kinetochore microtubules, analogous to a tug-of-war between two people of equal strength, ending with the destruction of B

cyclin Cyclins are proteins that control the progression of a cell through the cell cycle by activating cyclin-dependent kinases (CDK). Etymology Cyclins were originally discovered by R. Timothy Hunt in 1982 while studying the cell cycle of sea urch ...

. In order to prevent deleterious

nondisjunction 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 ...

events, a key

cell cycle checkpoint Cell cycle checkpoints are control mechanisms in the eukaryotic cell cycle which ensure its proper progression. Each checkpoint serves as a potential termination point along the cell cycle, during which the conditions of the cell are assessed, wi ...

, the

spindle 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 preven ...

, verifies this evenly balanced alignment and ensures that every kinetochore is properly attached to a bundle of microtubules and is under balanced bipolar tension. Sister chromatids require active

separase Separase, also known as separin, is a cysteine protease responsible for triggering anaphase by hydrolysing cohesin, which is the protein responsible for binding sister chromatids during the early stage of anaphase. In humans, separin is encode ...

to hydrolyze the

cohesin Cohesin is a protein complex that mediates Establishment of sister chromatid cohesion, sister chromatid cohesion, homologous recombination, and Topologically associating domain, DNA looping. Cohesin is formed of SMC3, SMC1A, SMC1, RAD21, SCC1 an ...

that bind them together prior to progression to

. Any unattached or improperly attached kinetochores generate signals that prevent the activation of the

anaphase promoting complex Anaphase-promoting complex (also called the cyclosome or APC/C) is an E3 ubiquitin ligase that marks target cell cycle proteins for degradation by the 26S proteasome. The APC/C is a large complex of 11–13 subunit proteins, including a cul ...

(cyclosome or APC/C), a

ubiquitin ligase A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin ...

which targets

securin Securin is a protein involved in control of the metaphase-anaphase transition and anaphase onset. Following bi-orientation of chromosome pairs and inactivation of the spindle checkpoint system, the underlying regulatory system, which includes securi ...

and

cyclin B Cyclin B is a member of the cyclin family. Cyclin B is a mitotic cyclin. The amount of cyclin B (which binds to Cdk1) and the activity of the cyclin B-Cdk complex rise through the cell cycle until mitosis, where they fall abruptly due to degr ...

for degradation via the

proteosome Proteasomes are essential protein complexes responsible for the degradation of proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are found inside all e ...

. As long as securin and cyclin B remain active, separase remains inactive, preventing premature progression to anaphase.

Metaphase in cytogenetics and cancer studies

The analysis of metaphase

s is one of the main tools of classical

cytogenetics Cytogenetics is essentially a branch of genetics, but is also a part of cell biology/cytology (a subdivision of human anatomy), that is concerned with how the chromosomes relate to cell behaviour, particularly to their behaviour during mitosis an ...

and

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

studies. Chromosomes are condensed (thickened) and highly coiled in metaphase, which makes them most suitable for visual analysis. Metaphase chromosomes make the classical picture of chromosomes (

karyotype A karyotype is the general appearance of the complete set of chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is discerned by de ...

). For classical cytogenetic analyses, cells are grown in short term culture and arrested in metaphase using

mitotic inhibitor A mitotic inhibitor, microtubule inhibitor, or tubulin inhibitor, is a drug that inhibits mitosis, or cell division, and is used in treating cancer, gout, and nail fungus. These drugs disrupt microtubules, which are structures that pull the chr ...

. Further they are used for slide preparation and banding (

staining Staining is a technique used to enhance contrast in samples, generally at the Microscope, microscopic level. Stains and dyes are frequently used in histology (microscopic study of biological tissue (biology), tissues), in cytology (microscopic ...

) of chromosomes to be visualised under microscope to study structure and number of chromosomes (karyotype).

Staining Staining is a technique used to enhance contrast in samples, generally at the Microscope, microscopic level. Stains and dyes are frequently used in histology (microscopic study of biological tissue (biology), tissues), in cytology (microscopic ...

of the slides, often with

Giemsa Giemsa stain (), named after German chemist and bacteriologist Gustav Giemsa, is a nucleic acid stain used in cytogenetics and for the histopathological diagnosis of malaria and other parasites. Uses It is specific for the phosphate groups of ...

(

G banding G-banding, G banding or Giemsa banding is a technique used in cytogenetics to produce a visible karyotype by staining condensed chromosomes. It is the most common chromosome banding method. It is useful for identifying genetic diseases (mainly chr ...

) or

Quinacrine Mepacrine, also called quinacrine or by the trade names Atabrine or Atebrin, is a medication with several uses. It is related to chloroquine and mefloquine. Although available from compounding pharmacies, as of August 2020 approved formulation ...

, produces a pattern of in total up to several hundred bands. Normal metaphase spreads are used in methods like

FISH A fish (: fish or fishes) is an aquatic animal, aquatic, Anamniotes, anamniotic, gill-bearing vertebrate animal with swimming fish fin, fins and craniate, a hard skull, but lacking limb (anatomy), limbs with digit (anatomy), digits. Fish can ...

and as a hybridization matrix for

comparative genomic hybridization Comparative genomic hybridization (CGH) is a molecular cytogenetic method for analysing copy number variations (CNVs) relative to ploidy level in the DNA of a test sample compared to a reference sample, without the need for culturing cells. The ai ...

(CGH) experiments.

Malignant cell Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not ...

s from solid

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s or

leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...

samples can also be used for cytogenetic analysis to generate metaphase preparations. Inspection of the stained metaphase chromosomes allows the determination of numerical and structural changes in the tumor cell genome, for example, losses of chromosomal segments or

translocations In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes "balanced" and "unbalanced" translocation, with three main types: "reciprocal", "nonreciprocal" and "Robertsonian" transloc ...

, which may lead to chimeric

oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

s, such as

bcr-abl The Philadelphia chromosome or Philadelphia translocation (Ph) is an abnormal version of chromosome 22 where a part of the '' Abelson murine leukemia'' 1 (''ABL1'') gene on chromosome 9 breaks off and attaches to the '' breakpoint cluster region'' ...

chronic myelogenous leukemia Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow and the accumula ...

References

External links

* {{Use dmy dates, date=April 2017 Mitosis Cell cycle de:Mitose#Metaphase