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''Schizosaccharomyces pombe'', also called "fission yeast", is a
species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...
of
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
used in traditional brewing and as a
model organism A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...
in
molecular A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...
and
cell biology Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and ...
. It is a unicellular
eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
, whose cells are rod-shaped. Cells typically measure 3 to 4
micrometre The micrometre ( international spelling as used by the International Bureau of Weights and Measures; SI symbol: μm) or micrometer (American spelling), also commonly known as a micron, is a unit of length in the International System of Unit ...
s in diameter and 7 to 14 micrometres in length. Its
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
, which is approximately 14.1 million base pairs, is estimated to contain 4,970 protein-coding
genes In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
and at least 450
non-coding RNAs A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non- ...
. These cells maintain their shape by growing exclusively through the cell tips and divide by medial fission to produce two daughter cells of equal size, which makes them a powerful tool in
cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...
research. Fission yeast was isolated in 1893 by
Paul Lindner Paul Lindner (1861 – 1945) was a German chemist and microbiologist, best known for discovering the fission yeast ''Schizosaccharomyces pombe''. Biography and career Lindner was born in 1861 in Giesmannsdorf near the Neisse River, part of Up ...
from East African
millet beer Millet beer, also known as Bantu beer, malwa, pombe "Tchouk" or opaque beer, is an alcoholic beverage made from malted millet that is common throughout Africa. Its production process varies across regions and in the southern parts of Africa ...
. The species name ''pombe'' is the Swahili word for beer. It was first developed as an experimental model in the 1950s: by Urs Leupold for studying genetics, and by
Murdoch Mitchison The Honounorable John Murdoch Mitchison FRS, FRSE (11 June 1922, Oxford – 17 March 2011, Edinburgh) was a British zoologist. Background Family Mitchison was the son of the Labour politician Dick Mitchison and his wife, the writer Naomi ...
for studying the cell cycle.
Paul Nurse Sir Paul Maxime Nurse (born 25 January 1949) is an English geneticist, former President of the Royal Society and Chief Executive and Director of the Francis Crick Institute. He was awarded the 2001 Nobel Prize in Physiology or Medicine along ...
, a fission yeast researcher, successfully merged the independent schools of fission yeast genetics and cell cycle research. Together with
Lee Hartwell Leland Harrison (Lee) Hartwell (born October 30, 1939 in Los Angeles, California) is former president and director of the Fred Hutchinson Cancer Research Center in Seattle, Washington (state), Washington. He shared the 2001 Nobel Prize in Physio ...
and
Tim Hunt Sir Richard Timothy Hunt, (born 19 February 1943) is a British biochemist and molecular physiologist. He was awarded the 2001 Nobel Prize in Physiology or Medicine with Paul Nurse and Leland H. Hartwell for their discoveries of protein molecu ...
, Nurse won the 2001
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
for their work on cell cycle regulation. The sequence of the ''S. pombe''
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
was published in 2002, by a consortium led by the
Sanger Institute The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit organisation, non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust. It is l ...
, becoming the sixth model eukaryotic organism whose
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
has been fully
sequenced In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which suc ...
. S. pombe researchers are supported by the
PomBase PomBase is a model organism database that provides online access to the fission yeast Schizosaccharomyces pombe genome sequence and annotated features, together with a wide range of manually curated functional gene-specific data. The PomBase webs ...
MOD (
model organism database Model organism databases (MODs) are biological databases, or knowledgebases, dedicated to the provision of in-depth biological data for intensively studied model organisms. MODs allow researchers to easily find background information on large sets ...
). This has fully unlocked the power of this organism, with many genes orthologous to human genes identified - 70% to date, including many genes involved in human disease. In 2006, sub-cellular localization of almost all the proteins in ''S. pombe'' was published using
green fluorescent protein The green fluorescent protein (GFP) is a protein that exhibits bright green fluorescence when exposed to light in the blue to ultraviolet range. The label ''GFP'' traditionally refers to the protein first isolated from the jellyfish ''Aequorea ...
as a molecular tag. ''Schizosaccharomyces pombe'' has also become an important organism in studying the cellular responses to
DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
and the process of
DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritanc ...
. Approximately 160 natural strains of ''S. pombe'' have been isolated. These have been collected from a variety of locations including Europe, North and South America, and Asia. The majority of these strains have been collected from cultivated fruits such as
apples An apple is an edible fruit produced by an apple tree (''Malus domestica''). Apple fruit tree, trees are agriculture, cultivated worldwide and are the most widely grown species in the genus ''Malus''. The tree originated in Central Asia, wh ...
and
grapes A grape is a fruit, botanically a berry, of the deciduous woody vines of the flowering plant genus ''Vitis''. Grapes are a non- climacteric type of fruit, generally occurring in clusters. The cultivation of grapes began perhaps 8,000 years ago ...
, or from the various
alcoholic beverage An alcoholic beverage (also called an alcoholic drink, adult beverage, or a drink) is a drink that contains ethanol, a type of alcohol that acts as a drug and is produced by fermentation of grains, fruits, or other sources of sugar. The c ...
s, such as Brazilian
Cachaça ''Cachaça'' () is a distilled spirit made from fermented sugarcane juice. Also known as ''pinga'', ''caninha'', and other names, it is the most popular spirit among distilled alcoholic beverages in Brazil.Cavalcante, Messias Soares. Todos os no ...
. ''S. pombe'' is also known to be present in fermented tea,
kombucha Kombucha (also tea mushroom, tea fungus, or Manchurian mushroom when referring to the culture; Latin name ''Medusomyces gisevii'') is a fermented, lightly effervescent, sweetened black tea drink commonly consumed for its purported health ben ...
. It is not clear at present whether ''S. pombe'' is the major fermenter or a contaminant in such brews. The natural ecology of ''
Schizosaccharomyces ''Schizosaccharomyces'' is a genus of fission yeasts. The most well-studied species is ''S. pombe''. At present five Schizosaccharomyces species have been described (''S. pombe'', ''S. japonicus'', ''S. octosporus'', ''S. cryophilus'' and ''S. ...
'' yeasts is not well-studied.


History

''Schizosaccharomyces pombe'' was first discovered in 1893 when a group working in a Brewery Association Laboratory in Germany was looking at sediment found in millet beer imported from East Africa that gave it an acidic taste. The term schizo, meaning "split" or "fission", had previously been used to describe other
Schizosaccharomycetes Schizosaccharomycetes is a class in the kingdom of fungi. It contains the order Schizosaccharomycetales, the fission yeasts. The genus Schizosaccharomycetes is a broad and ancient clade within Ascomycota including five known fission yeast: '' ...
. The addition of the word pombe was due to its isolation from East African beer, as pombe means "beer" in Swahili. The standard ''S. pombe'' strains were isolated by Urs Leupold in 1946 and 1947 from a culture that he obtained from the yeast collection in
Delft Delft () is a List of cities in the Netherlands by province, city and Municipalities of the Netherlands, municipality in the Provinces of the Netherlands, province of South Holland, Netherlands. It is located between Rotterdam, to the southeast, ...
, The Netherlands. It was deposited there by A. Osterwalder under the name ''S. pombe'' var. ''liquefaciens'', after he isolated it in 1924 from French wine (most probably rancid) at the Federal Experimental Station of Vini- and Horticulture in
Wädenswil Wädenswil, locally often called ''Wädi'' or ''Wädischwil,'' is a municipality located in the district of Horgen in the canton of Zürich in Switzerland. The population, , was about 21,000. On 1 January 2019 the former municipalities of Hü ...
, Switzerland. The culture used by Urs Leupold contained (besides others) cells with the mating types h90 (strain 968), h- (strain 972), and h+ (strain 975). Subsequent to this, there have been two large efforts to isolate ''S. pombe'' from fruit, nectar, or fermentations: one by Florenzano et al. in the vineyards of western Sicily, and the other by Gomes et al. (2002) in four regions of southeast Brazil.


Ecology

The fission yeast ''S. pombe'' belongs to the divisio Ascomycota, which represents the largest and most diverse group of fungi. Free-living ascomycetes are commonly found in tree exudates, on plant roots and in surrounding soil, on ripe and rotting fruits, and in association with insect vectors that transport them between substrates. Many of these associations are symbiotic or saprophytic, although numerous ascomycetes (and their basidiomycete cousins) represent important plant pathogens that target myriad plant species, including commercial crops. Among the ascomycetous yeast genera, the fission yeast ''Schizosaccharomyces'' is unique because of the deposition of α-(1,3)-glucan or pseudonigeran in the cell wall in addition to the better known β-glucans and the virtual lack of chitin. Species of this genus also differ in mannan composition, which shows terminal d-galactose sugars in the side-chains of their mannans. ''S. pombe'' undergo
aerobic fermentation Aerobic fermentation or aerobic glycolysis is a metabolic process by which cells metabolize sugars via fermentation in the presence of oxygen and occurs through the repression of normal respiratory metabolism. It is referred to as the Crabtree effec ...
in the presence of excess sugar. ''S. pombe'' can degrade L-malic acid, one of the dominant organic acids in wine, which makes them diverse among other ''Saccharomyces'' strains.


Comparison with budding yeast (''Saccharomyces cerevisiae'')

The yeast species ''Schizosaccharomyces pombe'' and ''
Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
'' are both extensively studied; these two species diverged approximately 300 to 600 million years before present, and are significant tools in molecular and cellular biology. Some of the technical discriminants between these two species are: * ''S. cerevisiae'' has approximately 5,600
open reading frame In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...
s; ''S. pombe'' has approximately 5,070 open reading frames. * Despite similar gene numbers, ''S. cerevisiae'' has only about 250
intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene. ...
s, while ''S. pombe'' has nearly 5,000. * ''S. cerevisiae'' has 16
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
s, ''S. pombe'' has 3. * ''S. cerevisiae'' is often
diploid Ploidy () is the number of complete sets of chromosomes in a cell, and hence the number of possible alleles for autosomal and pseudoautosomal genes. Sets of chromosomes refer to the number of maternal and paternal chromosome copies, respectively ...
while ''S. pombe'' is usually
haploid Ploidy () is the number of complete sets of chromosomes in a cell, and hence the number of possible alleles for autosomal and pseudoautosomal genes. Sets of chromosomes refer to the number of maternal and paternal chromosome copies, respectively ...
. * ''S. pombe'' has a
shelterin Shelterin (also called telosome) is a protein complex known to protect telomeres in many eukaryotes from DNA repair mechanisms, as well as to regulate telomerase activity. In mammals and other vertebrates, telomeric DNA consists of repeating double ...
-like
telomere A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...
complex while ''S. cerevisiae '' does not. * ''S. cerevisiae'' is in the G1 phase of the
cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...
for an extended period (as a consequence, G1-S transition is tightly controlled), while ''S. pombe'' remains in the G2 phase of the cell cycle for an extended period (as a consequence, G2-M transition is under tight control). * Both species share genes with higher eukaryotes that they do not share with each other. ''S. pombe'' has RNAi machinery genes like those in vertebrates, while this is missing from ''S. cerevisiae''. ''S. cerevisiae'' also has greatly simplified heterochromatin compared to ''S. pombe''. Conversely, ''S. cerevisiae'' has well-developed
peroxisomes A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen pero ...
, while ''S. pombe'' does not. * ''S. cerevisiae'' has small point
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 fibers a ...
of 125 bp, and sequence-defined replication origins of about the same size. On the converse, ''S. pombe'' has large, repetitive centromeres (40–100 kb) more similar to mammalian centromeres, and degenerate replication origins of at least 1kb.


S. pombe pathways and cellular processes

''S. pombe'' gene products (proteins and RNAs) participate in many cellular processes common across all life. Th
fission yeast GO slim
provides a categorical high level overview of the biological role of all S. pombe gene products.


Life cycle

The fission yeast is a single-celled fungus with simple, fully characterized genome and a rapid growth rate. It has long been used in brewing, baking, and molecular genetics. ''S. pombe'' is a rod-shaped cell, approximately 3 μm in diameter, that grows entirely by elongation at the ends. After mitosis, division occurs by the formation of a septum, or cell plate, that cleaves the cell at its midpoint. The central events of cell reproduction are chromosome duplication, which takes place in S (Synthetic) phase, followed by chromosome segregation and nuclear division (mitosis) and cell division (cytokinesis), which are collectively called M (Mitotic) phase. G1 is the gap between M and S phases, and G2 is the gap between S and M phases. In the fission yeast, the G2 phase is particularly extended, and cytokinesis (daughter-cell segregation) does not happen until a new S (Synthetic) phase is launched. Fission yeast governs mitosis by mechanisms that are similar to those in multicellular animals. It normally proliferates in a haploid state. When starved, cells of opposite mating types (P and M) fuse to form a diploid zygote that immediately enters meiosis to generate four haploid spores. When conditions improve, these spores germinate to produce proliferating haploid cells. Image:general_cell_cycle.jpg, General features of the cell cycle. Image:fission_yeast_cell_cycle_structure.jpg, The particular cell cycle of a fission yeast. Image:Schizosaccharomyces pombe division.JPG, Division stages of ''Schizosaccharomyces'' in bright and dark field light microscopy


Cytokinesis

The general features of cytokinesis are shown here. The site of cell division is determined before anaphase. The anaphase spindle (in green on the figure) is then positioned so that the segregated chromosomes are on opposite sides of the predetermined cleavage plane.


Size control

In fission yeast, where growth governs progression through G2/M, a
wee1 Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast ''Schizosaccharomyces pombe'' (''S. pombe'')Wee1has a molecular mass of 96 kDa and is a key regulator of cell cycle progression. It influences ...
mutation causes entry into mitosis at an abnormally small size, resulting in a shorter G2. G1 is lengthened, suggesting that progression through Start (beginning of cell cycle) is responsive to growth when the G2/M control is lost. Furthermore, cells in poor nutrient conditions grow slowly and therefore take longer to double in size and divide. Low nutrient levels also reset the growth threshold so that cell progresses through the cell cycle at a smaller size. Upon exposure to stressful conditions eat (40 °C) or the oxidizing agent hydrogen peroxide''S. pombe'' cells undergo
aging Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...
as measured by increased cell division time and increased probability of cell death. Finally, wee1 mutant fission yeast cells are smaller than wild-type cells, but take just as long to go through the cell cycle. This is possible because small yeast cells grow slower, that is, their added total mass per unit time is smaller than that of normal cells. A spatial gradient is thought to coordinate cell size and mitotic entry in fission yeast. The
Pom1 Pom1 is a polarity protein kinase in fission yeast, ''Schizosaccharomyces pombe'' (''S. pombe''), that localizes to cell ends and regulates cell division. As the cell lengthens, the level of Pom1 in the middle declines, which triggers mitosis.Bahle ...
protein kinase (green) is localized to the cell cortex, with the highest concentration at the cell tips. The cell-cycle regulators Cdr2, Cdr1 and Wee1 are present in cortical nodes in the middle of the cell (blue and red dots). a, In small cells, the
Pom1 Pom1 is a polarity protein kinase in fission yeast, ''Schizosaccharomyces pombe'' (''S. pombe''), that localizes to cell ends and regulates cell division. As the cell lengthens, the level of Pom1 in the middle declines, which triggers mitosis.Bahle ...
gradient reaches most of the cortical nodes (blue dots).
Pom1 Pom1 is a polarity protein kinase in fission yeast, ''Schizosaccharomyces pombe'' (''S. pombe''), that localizes to cell ends and regulates cell division. As the cell lengthens, the level of Pom1 in the middle declines, which triggers mitosis.Bahle ...
inhibits Cdr2, preventing Cdr2 and Cdr1 from inhibiting Wee1, and allowing Wee1 to phosphorylate Cdk1, thus inactivating cyclin-dependent kinase (CDK) activity and preventing entry into mitosis. b, In long cells, the
Pom1 Pom1 is a polarity protein kinase in fission yeast, ''Schizosaccharomyces pombe'' (''S. pombe''), that localizes to cell ends and regulates cell division. As the cell lengthens, the level of Pom1 in the middle declines, which triggers mitosis.Bahle ...
gradient does not reach the cortical nodes (red dots), and therefore Cdr2 and Cdr1 remain active in the nodes. Cdr2 and Cdr1 inhibit Wee1, preventing phosphorylation of Cdk1 and thereby leading to activation of CDK and mitotic entry. (This simplified diagram omits several other regulators of CDK activity.)


Mating-type switching

Fission yeast switches mating type by a replication-coupled recombination event, which takes place during S phase of the cell cycle. Fission yeast uses intrinsic asymmetry of the DNA replication process to switch the mating type; it was the first system where the direction of replication was shown to be required for the change of the cell type. Studies of the mating-type switching system lead to a discovery and characterization of a site-specific replication termination site RTS1, a site-specific replication pause site MPS1, and a novel type of chromosomal imprint, marking one of the sister chromatids at the mating-type locus mat1. In addition, work on the silenced donor region has led to great advances in understanding formation and maintenance of heterochromatin.


Responses to DNA damage

''Schizosaccharomyces pombe'' is a facultative sexual microorganism that can undergo mating when nutrients are limiting. Exposure of ''S. pombe'' to hydrogen peroxide, an agent that causes
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...
leading to oxidative
DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
, strongly induces
mating In biology, mating is the pairing of either opposite-sex or hermaphroditic organisms for the purposes of sexual reproduction. ''Fertilization'' is the fusion of two gametes. ''Copulation'' is the union of the sex organs of two sexually reproduc ...
and formation of meiotic spores. This finding suggests that meiosis, and particularly meiotic recombination, may be an adaptation for repairing DNA damage. Supporting this view is the finding that single base lesions of the type dU:dG in the DNA of ''S. pombe'' stimulate meiotic recombination. This recombination requires
uracil-DNA glycosylase Uracil-DNA glycosylase is also known as UNG or UDG. Its most important function is to prevent mutagenesis by eliminating uracil from DNA molecules by cleaving the N-glycosidic bond and initiating the base-excision repair (BER) pathway. Function ...
, an enzyme that removes uracil from the DNA backbone and initiates base excision repair. On the basis of this finding, it was proposed that base excision repair of either a uracil base, an abasic site, or a single-strand nick is sufficient to initiate recombination in S. pombe. Other experiments with ''S. pombe'' indicated that faulty processing of DNA replication intermediates, i.e.
Okazaki fragments Okazaki fragments are short sequences of DNA nucleotides (approximately 150 to 200 base pairs long in eukaryotes) which are synthesized discontinuously and later linked together by the enzyme DNA ligase to create the lagging strand during DNA ...
, causes DNA damages such as single-strand nicks or gaps, and that these stimulate meiotic recombination.


As a model system

Fission yeast has become a notable model system to study basic principles of a cell that can be used to understand more complex organisms like mammals and in particular humans. This single cell eukaryote is nonpathogenic and easily grown and manipulated in the lab. Fission yeast contains one of the smallest numbers of genes of a known genome sequence for a eukaryote, and has only three chromosomes in its genome. Many of the genes responsible for cell division and cellular organization in fission yeast cell are also found in the human's genome. Cell cycle regulation and division are crucial for growth and development of any cell. Fission yeast's conserved genes has been heavily studied and the reason for many recent biomedical developments. Fission yeast is also a practical model system to observe cell division because fission yeast's are cylindrically shaped single celled eukaryotes that divide and reproduce by medial fission. This can easily be seen using microscopy. Fission yeast also have an extremely short generation time, 2 to 4 hours, which also makes it an easy model system to observe and grow in the laboratory Fission yeast's simplicity in genomic structure yet similarities with mammalian genome, ease of ability to manipulate, and ability to be used for drug analysis is why fission yeast is making many contributions to biomedicine and cellular biology research, and a model system for genetic analysis.


Genome

''Schizosaccharomyces pombe'' is often used to study cell division and growth because of conserved genomic regions also seen in humans including: heterochromatin proteins, large origins of replication, large centromeres, conserved cellular checkpoints, telomere function, gene splicing, and many other cellular processes. ''S. pombe''s genome was fully sequenced in 2002, the sixth eukaryotic genome to be sequenced as part of the Genome Project. An estimated 4,979 genes were discovered within three chromosomes containing about 14Mb of DNA. This DNA is contained within 3 different chromosomes in the nucleus with gaps in the centromeric (40kb) and telomeric (260kb) regions. After the initial sequencing of the fission yeast's genome, other previous non-sequenced regions of the genes have been sequenced. Structural and functional analysis of these gene regions can be found on large scale fission yeast databases such as
PomBase PomBase is a model organism database that provides online access to the fission yeast Schizosaccharomyces pombe genome sequence and annotated features, together with a wide range of manually curated functional gene-specific data. The PomBase webs ...
. Forty-three percent of the genes in the Genome Project were found to contain introns in 4,739 genes. Fission yeast does not have as many duplicated genes compared to budding yeast, only containing 5%, making fission yeast a great model genome to observe and gives researchers the ability to create more functional research approaches. ''S. pombe''s having a large number of introns gives opportunities for an increase of range of protein types produced from alternative splicing and genes that code for comparable genes in human. 81% of the three centromeres in fission yeast have been sequenced. The lengths of the three centromeres were found to be 34, 65, and 110 kb. This is 300–100 times longer than the centromeres of budding yeast. An extremely high level of conservation (97%) is also seen over 1,780-bp region in the DGS regions of the centromere. This elongation of centromeres and its conservative sequences makes fission yeast a practical model system to use to observe cell division and in humans because of their likeness.
PomBase PomBase is a model organism database that provides online access to the fission yeast Schizosaccharomyces pombe genome sequence and annotated features, together with a wide range of manually curated functional gene-specific data. The PomBase webs ...
reports over 69% of protein coding genes hav
human orthologs
and over 500 of these ar
associated with human disease
. This makes ''S. pombe'' a great system to use to study human genes and disease pathways, especially cell cycle and DNA checkpoint systems.


Genetic diversity

Biodiversity and evolutionary study of fission yeast was carried out on 161 strains of Schizosaccharomyces pombe collected from 20 countries. Modeling of the evolutionary rate showed that all strains derived from a common ancestor that has lived since ~2,300 years ago. The study also identified a set of 57 strains of fission yeast that each differed by ≥1,900 SNPs;, and all detected 57 strains of fission yeast were prototrophic (able to grow on the same minimal medium as the reference strain). A number of studies on S.pombe genome support the idea that the genetic diversity of fission yeast strains is slightly less than budding yeast. Indeed, only limited variations of S.pombe occur in proliferation in different environments. In addition, the amount of phenotypic variation segregating in fission yeast is less than that seen, in S. cerevisiae. Since most strains of fission yeast were isolated from brewed beverages, there is no ecological or historical context to this dispersal.


Cell cycle analysis

DNA replication in yeast has been increasingly studied by many researchers. Further understanding of DNA replication, gene expression, and conserved mechanisms in yeast can provide researchers with information on how these systems operate in mammalian cells in general and human cells in particular. Other stages, such as cellular growth and aging, are also observed in yeast in order to understand these mechanisms in more complex systems. ''S. pombe'' stationary phase cells undergo chronological
aging Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...
due to production of
reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...
that cause DNA damages. Most such damages can ordinarily be repaired by DNA
base excision repair Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from t ...
and
nucleotide excision repair Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals (e.g. intercalating agents), radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucle ...
. Defects in these repair processes lead to reduced survival. Cytokinesis is one of the components of cell division that is often observed in fission yeast. Well-conserved components of cytokinesis are observed in fission yeast and allow us to look at various genomic scenarios and pinpoint mutations. Cytokinesis is a permanent step and very crucial to the wellbeing of the cell. Contractile ring formation in particular is heavily studied by researchers using ''S. pombe'' as a model system. The contractile ring is highly conserved in both fission yeast and human cytokinesis. Mutations in cytokinesis can result in many malfunctions of the cell including cell death and development of cancerous cells. This is a complex process in human cell division, but in ''S. pombe'' simpler experiments can yield results that can then be applied for research in higher-order model systems such as humans. One of the safety precautions that the cell takes to ensure precise cell division occurs is the cell-cycle checkpoint. These checkpoints ensure any mutagens are eliminated. This is done often by relay signals that stimulate ubiquitination of the targets and delay cytokinesis. Without mitotic check points such as these, mutagens are created and replicated, resulting in multitudes of cellular issues including cell death or tumorigenesis seen in cancerous cells. Paul Nurse, Leland Hartwell, and Tim Hunt were awarded the Nobel Prize in Physiology or Medicine in 2001. They discovered key conserved checkpoints that are crucial for a cell to divide properly. These findings have been linked to cancer and diseased cells and are a notable finding for biomedicine. Researchers using fission yeast as a model system also look at organelle dynamics and responses and the possible correlations between yeast cells and mammalian cells. Mitochondria diseases, and various organelle systems such as the Golgi apparatus and endoplasmic reticulum, can be further understood, by observing fission yeast's chromosome dynamics and protein expression levels and regulation.


Biomedical tool

However, there are limitations with using fission yeast as a model system: its multidrug resistance. "The MDR response involves overexpression of two types of drug efflux pumps, the ATP-binding cassette (ABC) family... and the major facilitator superfamily". Paul Nurse and some of his colleagues have recently created ''S. pombe'' strains sensitive to chemical inhibitors and common probes to see whether it is possible to use fission yeast as a model system of chemical drug research. For example, Doxorubicin, a very common chemotherapeutic antibiotic, has many adverse side-effects. Researchers are looking for ways to further understand how doxorubicin works by observing the genes linked to resistance by using fission yeast as a model system. Links between doxorubicin adverse side-effects and chromosome metabolism and membrane transport were seen. Metabolic models for drug targeting are now being used in biotechnology, and further advances are expected in the future using the fission yeast model system.


Experimental approaches

Fission yeast is easily accessible, easily grown and manipulated to make mutants, and able to be maintained at either a haploid or diploid state. ''S. pombe'' is normally a haploid cell but, when put under stressful conditions, usually nitrogen deficiency, two cells will conjugate to form a diploid that later form four spores within a tetrad ascus. This process is easily visible and observable under any microscope and allows us to look at meiosis in a simpler model system to see how this phenomenon operates. Virtually any genetics experiment or technique can, therefore, be applied to this model system such as: tetrad dissection, mutagens analysis, transformations, and microscopy techniques such as FRAP and FRET. New models, such as Tug-Of-War (gTOW), are also being used to analyze yeast robustness and observe gene expression. Making knock-in and knock-out genes is fairly easy and with the fission yeast's genome being sequenced this task is very accessible and well known.


See also

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DNA damage (naturally occurring) DNA damage is an alteration in the chemical structure of DNA, such as a break in a strand of DNA, a nucleobase missing from the backbone of DNA, or a chemically changed base such as 8-OHdG. DNA damage can occur naturally or via environmental fac ...
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DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...
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Yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
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PomBase PomBase is a model organism database that provides online access to the fission yeast Schizosaccharomyces pombe genome sequence and annotated features, together with a wide range of manually curated functional gene-specific data. The PomBase webs ...


References


External links


PomBase - The Pombe Genome Database

MicrobeWiki page on Schizosaccharomyces pombe
{{DEFAULTSORT:Schizosaccharomyces Pombe Ascomycota Fungal models Yeasts Fungi described in 1893 ru:Делящиеся дрожжи