condensin
   HOME

TheInfoList



OR:

Condensins are large
protein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain. Protein ...
es that play a central role in
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 ...
assembly and segregation during mitosis and
meiosis Meiosis (; , since it is a reductional division) 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 resu ...
(Figure 1). Their subunits were originally identified as major components of mitotic chromosomes assembled in ''Xenopus'' egg extracts.


Subunit composition


Eukaryotic types

Many
eukaryotic Eukaryotes () are organisms whose Cell (biology), cells have a cell nucleus, 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 ...
cells possess two different types of condensin complexes, known as condensin I and condensin II, each of which is composed of five subunits (Figure 2). Condensins I and II share the same pair of core subunits, SMC2 and SMC4, both belonging to a large family of chromosomal
ATPases ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...
, known as
SMC proteins SMC complexes represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes. Classification Eukaryotic SMCs Eukaryotes have at l ...
(SMC stands for Structural Maintenance of Chromosomes). Each of the complexes contains a distinct set of non-SMC regulatory subunits (a kleisin subunit and a pair of
HEAT repeat A HEAT repeat is a protein tandem repeat structural motif composed of two alpha helices linked by a short loop. HEAT repeats can form alpha solenoids, a type of solenoid protein domain found in a number of cytoplasmic proteins. The name "HEAT" ...
subunits). Both complexes are large, having a total
molecular mass The molecular mass (''m'') is the mass of a given molecule: it is measured in daltons (Da or u). Different molecules of the same compound may have different molecular masses because they contain different isotopes of an element. The related quanti ...
of 650-700 kDa. The core subunits condensins (SMC2 and SMC4) are conserved among all
eukaryotic Eukaryotes () are organisms whose Cell (biology), cells have a cell nucleus, 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 ...
species that have been studied to date. The non-SMC subunits unique to condensin I are also conserved among eukaryotes, but the occurrence of the non-SMC subunits unique to condensin II is highly variable among species. *For instance, the fruit fly ''
Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...
'' does not have the gene for the CAP-G2 subunit of condensin II. Other insect species often lack the genes for the CAP-D3 and/or CAP-H subunits, too, indicating that the non-SMC subunits unique to condensin II have been under high
selection pressure Any cause that reduces or increases reproductive success in a portion of a population potentially exerts evolutionary pressure, selective pressure or selection pressure, driving natural selection. It is a quantitative description of the amount of ...
during insect evolution. *The nematode '' Caenorhabditis elegans'' possesses both condensins I and II. This species is, however, unique in the sense that it has a third complex (closely related to condensin I) that participates in chromosome-wide
gene regulation Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wi ...
, i.e.,
dosage compensation Dosage compensation is the process by which organisms equalize the expression of genes between members of different biological sexes. Across species, different sexes are often characterized by different types and numbers of sex chromosomes. In order ...
. In this complex, known as condensin IDC, the authentic SMC4 subunit is replaced with its variant, DPY-27 (Figure 2). *Some species, like
fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
(e.g., the budding yeast ''
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 b ...
'' and the fission yeast ''
Schizosaccharomyces pombe ''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measur ...
''), lack all regulatory subunits unique to condensin II. On the other hand, the unicellular, primitive red alga ''
Cyanidioschyzon merolae ''Cyanidioschyzon merolae'' is a small (2μm), club-shaped, unicellular haploid red alga adapted to high sulfur acidic hot spring environments (pH 1.5, 45 °C). The cellular architecture of ''C. merolae'' is extremely simple, containing only ...
'', whose genome size is comparable to those of the yeast, has both condensins I and II. Thus, there is no apparent relationship between the occurrence of condensin II and the size of eukaryotic genomes. *The
ciliate The ciliates are a group of alveolates characterized by the presence of hair-like organelles called cilia, which are identical in structure to eukaryotic flagella, but are in general shorter and present in much larger numbers, with a differen ...
''
Tetrahymena thermophila ''Tetrahymena thermophila'' is a species of Ciliophora in the family Tetrahymenidae. It is a free living protozoa and occurs in fresh water. There is little information on the ecology and natural history of this species, but it is the most wi ...
'' has condensin I only. Nevertheless, there are multiple
paralogs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a sp ...
for two of its regulatory subunits (CAP-D2 and CAP-H), and some of them specifically localize to either the
macronucleus A macronucleus (formerly also meganucleus) is the larger type of nucleus in ciliates. Macronuclei are polyploid and undergo direct division without mitosis. It controls the non-reproductive cell functions, such as metabolism. During conjugation, ...
(responsible for gene expression) or the
micronucleus Micronucleus is the name given to the small nucleus that forms whenever a chromosome or a fragment of a chromosome is not incorporated into one of the daughter nuclei during cell division. It usually is a sign of genotoxic events and chromosomal i ...
(responsible for reproduction). Thus, this species has multiple condensin I complexes that have different regulatory subunits and display distinct nuclear localization. This is a very unique property that is not found in other species.


Prokaryotic types

Prokaryotic A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
species also have condensin-like complexes that play an important role in chromosome ( nucleoid) organization and segregation. The prokaryotic condensins can be classified into two types: SMC-ScpAB and MukBEF. Many eubacterial and archaeal species have SMC-ScpAB, whereas a subgroup of eubacteria (known as Gammaproteobacteria) including ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'' has MukBEF. ScpA and MukF belong to a family of proteins called "kleisins", whereas ScpB and MukF have recently been classified into a new family of proteins named "kite". Despite highly divergent primary structures of their corresponding subunits between SMC-ScpAB and MukBEF, it is reasonable to consider that the two complexes play similar if not identical functions in prokaryotic chromosome organization and dynamics, based on their molecular architecture and their defective cellular phenotypes. Both complexes are therefore often called prokaryotic (or bacterial) condensins. Recent studies report the occurrence of a third complex related to MukBEF (termed MksBEF) in some bacterial species.


Molecular mechanisms


Molecular structures

SMC dimers that act as the core subunits of condensins display a highly characteristic V-shape, each arm of which is composed of anti-parallel coiled-coils (Figure 3; see
SMC proteins SMC complexes represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes. Classification Eukaryotic SMCs Eukaryotes have at l ...
for details). The length of each coiled-coil arm reaches ~50 nm, which corresponds to the length of ~150 bp of double-stranded DNA (dsDNA). In eukaryotic condensin I and II complexes, a kleisin subunit bridges the two head domains of an SMC dimer, and binds to two HEAT repeat subunits (Figure 1). Early studies elucidated the structure of parts of bacterial condensins, such as MukBEF and SMC-ScpA. In eukaryotic complexes, several structures of subcomplexes and subdomains have been reported, including the hinge and arm domains of an SMC2-SMC4 dimer, a CAP-G(ycg1)/CAP-H(brn1) subcomplex, and a CAP-D2(ycs4)/CAP-H(brn1) subcomplex. A recent cryo-EM study has shown that condensin undergoes large conformational changes that are coupled with ATP-binding and hydrolysis by its SMC subunits. On the other hand, fast-speed atomic force microscopy has demonstrated that the arms of an SMC dimer is far more flexible than was expected.


Molecular activities

Condensin I purified from ''Xenopus'' egg extracts is a DNA-stimulated ATPase and displays the ability to introduce positive superhelical tension into dsDNA in an ATP-hydrolysis-dependent manner (positive supercoiling activity). Similar activities have been detected in condensins from other organisms. The positive supercoiling activity is activated ''in vitro'' by
Cdk1 Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in t ...
phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
, suggesting that it is likely one of the physiological activities directly involved in mitotic chromosome assembly. It is postulated that this activity of condensin I helps fold DNA and promotes
topoisomerase II Type II topoisomerases are topoisomerases that cut both strands of the DNA helix simultaneously in order to manage DNA tangles and supercoils. They use the hydrolysis of ATP, unlike Type I topoisomerase. In this process, these enzymes change th ...
-mediated resolution of sister chromatids. Early single-DNA-molecule experiments also demonstrated in real time that condensin I is able to compact DNA in an ATP-hydrolysis dependent manner. Most recently, single-molecule experiments have demonstrated that budding yeast condensin I is able to translocate along dsDNA (
motor An engine or motor is a machine designed to convert one or more forms of energy into mechanical energy. Available energy sources include potential energy (e.g. energy of the Earth's gravitational field as exploited in hydroelectric power g ...
activity) and to "extrude" DNA loops ( loop extrusion activity) in an ATP hydrolysis-dependent manner. In the latter experiments, the activity of individual condensin complexes on DNA was visualized by real-time
fluorescence imaging Fluorescence imaging is a type of non-invasive imaging technique that can help visualize biological processes taking place in a living organism. Images can be produced from a variety of methods including: microscopy, imaging probes, and spectrosco ...
, revealing that condensin I indeed is a fast loop-extruding motor and that a single condensin I complex can extrude 1,500 bp of DNA per second in a strictly ATP-dependent manner. It has been proposed that condensin I anchors DNA between Ycg1-Brn1 subunits and pulls DNA asymmetrically to form large loops. Moreover, it has been shown that condensin complexes can traverse each other, forming dynamic loop structures and changing their sizes. It is unknown how condensins might act on nucleosomal DNA. Recent development of a reconstitution system has identified the
histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn a ...
chaperone FACT as an essential component of condensin I-mediated chromosome assembly ''in vitro'', providing an important clue to this problem. It has also been shown that condensins can assemble chromosome-like structures in cell-free extracts even under the condition where nucleosome assembly is largely suppressed. This observation indicates that condensins can work at least in part on non-nucleosomal DNA in a physiological setting. Only limited information is currently available as to the functional contribution of individual subunits of condensins to their activities. An SMC2-SMC4 dimer has an ability to reanneal complementary single-stranded DNA. This activity does not require ATP. For eukaryotic complexes, it has been reported that
HEAT repeat A HEAT repeat is a protein tandem repeat structural motif composed of two alpha helices linked by a short loop. HEAT repeats can form alpha solenoids, a type of solenoid protein domain found in a number of cytoplasmic proteins. The name "HEAT" ...
subunits contribute to part of DNA binding and to the assembly of chromosome axes. Flexible and extendable nature of HEAT repeats could underlie the dynamic action of condensins and the architecture of mitotic chromosomes.


Mathematical modeling

Several attempts on mathematical modeling and
computer simulation Computer simulation is the process of mathematical modelling, performed on a computer, which is designed to predict the behaviour of, or the outcome of, a real-world or physical system. The reliability of some mathematical models can be dete ...
of mitotic chromosome assembly, based on molecular activities of condensins, have been reported. Representative ones include modeling based on loop extrusion, stochastic pairwise contacts and a combination of looping and inter-condensin attractions.


Functions in chromosome assembly and segregation


Mitosis

In human tissue culture cells, the two condensin complexes are regulated differently during the
mitotic In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maintai ...
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 sub ...
(Figure 4). Condensin II is present within the cell nucleus during
interphase Interphase is the portion of the cell cycle that is not accompanied by visible changes under the microscope, and includes the G1, S and G2 phases. During interphase, the cell grows (G1), replicates its DNA (S) and prepares for mitosis (G2). A c ...
and participates in an early stage of chromosome condensation within the
prophase 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 ret ...
nucleus. On the other hand, condensin I is present in the
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
during interphase, and gains access to chromosomes only after the nuclear envelope breaks down (NEBD) at the end of prophase. During
prometaphase Prometaphase is the phase of mitosis following prophase and preceding metaphase, in eukaryote, eukaryotic Somatic (biology), somatic Cell (biology), cells. In prometaphase, the nuclear membrane breaks apart into numerous "membrane vesicles", ...
and
metaphase Metaphase ( and ) is a stage of mitosis in the eukaryotic cell cycle in which chromosomes are at their second-most condensed and coiled stage (they are at their most condensed in anaphase). These chromosomes, carrying genetic information, alig ...
, condensin I and condensin II cooperate to assemble rod-shaped chromosomes, in which two
sister chromatids 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 dup ...
are fully resolved. Such differential dynamics of the two complexes is observed in ''Xenopus'' egg extracts, mouse oocytes, and neural stem cells, indicating that it is part of a fundamental regulatory mechanism conserved among different organisms and cell types. It is most likely that this mechanism ensures the ordered action of the two complexes, namely, condensin II first and condensin I later. On
metaphase Metaphase ( and ) is a stage of mitosis in the eukaryotic cell cycle in which chromosomes are at their second-most condensed and coiled stage (they are at their most condensed in anaphase). These chromosomes, carrying genetic information, alig ...
chromosomes, condensins I and II are both enriched in the central axis in a non-overlapping fashion (Figure 5). Depletion experiments ''in vivo'' and immunodepletion experiments in ''Xenopus'' egg extracts demonstrate that the two complexes have distinct functions in assembling metaphase chromosomes. Cells deficient in condensin functions are not arrested at a specific stage of cell cycle, displaying chromosome segregation defects (i.e., anaphase bridges) and progressing through abnormal cytokinesis. The relative contribution of condensins I and II to mitosis varies among different eukaryotic species. For instance, each of condensins I and II plays an essential role in embryonic development in mice. They have both overlapping and non-overlapping functions during the mitotic cell cycle. On the other hand, condensin II is non-essential for mitosis in the primitive alga '' C. merolae'' and the land plant ''
A. thaliana ''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small flowering plant native to Eurasia and Africa. ''A. thaliana'' is considered a weed; it is found along the shoulders of roads and in disturbed land. A winter a ...
''. Curiously, condensin II plays a dominant role over condensin I in the ''
C. elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
'' early embryos. This peculiarity could be due to the fact that ''
C. elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
'' has a specialized chromosome structure known as
holocentric chromosomes Holocentric chromosomes are chromosomes that possess multiple kinetochores along their length rather than the single centromere typical of other chromosomes. They were first described in cytogenetic experiments in 1935. Since this first observation, ...
. Fungi, such as ''
S. 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 bee ...
'' and ''
S. pombe ''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measur ...
'' have no condensin II from the first. These differences among eukaryotic species provide important implications in the evolution of chromosome architecture (see the section of "Evolutionary implications" below). It has recently become possible that cell cycle-dependent structural changes of chromosomes are monitored by a genomics-based method known as Hi-C (High-throughput
chromosome conformation capture Chromosome conformation capture techniques (often abbreviated to 3C technologies or 3C-based methods) are a set of molecular biology methods used to analyze the spatial organization of chromatin in a cell. These methods quantify the number of int ...
). The impact of condensin deficiency on chromosome conformation has been addressed in budding yeast, fission yeast, and the chicken DT40 cells. The outcome of these studies strongly supports the notion that condensins play crucial roles in mitotic chromosome assembly and that condensin I and II have distinct functions in this process. Moreover, quantitative imaging analyses allow researchers to count the number of condensin complexes present on human metaphase chromosomes.


Meiosis

Condensins also play important roles in chromosome assembly and segregation in
meiosis Meiosis (; , since it is a reductional division) 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 resu ...
. Genetic studies have been reported in ''
S. 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 bee ...
,'' ''
D. melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...
,'' and ''
C. elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
''. In mice, requirements for condensin subunits in meiosis have been addressed by antibody-mediated blocking experiments and
conditional gene knockout Conditional gene knockout is a technique used to eliminate a specific gene in a certain tissue, such as the liver. This technique is useful to study the role of individual genes in living organisms. It differs from traditional gene knockout because ...
analyses. In mammalian meiosis I, the functional contribution of condensin II appears bigger than that of condensin I. As has been shown in mitosis, however, the two condensin complexes have both overlapping and non-overlapping functions, too, in meiosis. Unlike
cohesin Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping. Cohesin is formed of SMC3, SMC1, SCC1 and SCC3 ( SA1 or SA2 in humans). Cohesin holds sister chromatids together after DNA rep ...
, no meiosis-specific subunits of condensins have been identified so far.


Chromosomal functions outside of mitosis or meiosis

Recent studies have shown that condensins participate in a wide variety of chromosome functions outside of mitosis or
meiosis Meiosis (; , since it is a reductional division) 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 resu ...
. *In
budding yeast ''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 ...
, condensin I (the sole condensin in this organism) is involved in copy number regulation of the rDNA repeat as well as in clustering of the
tRNA Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ac ...
genes. *In
fission yeast ''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically m ...
, condensin I is involved in the regulation of replicative checkpoint and clustering of genes transcribed by RNA polymerase III. *In ''
C. elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
'', a third condensin complex (condensin IDC) related to condensin I regulates higher-order structure of X chromosomes as a major regulator of
dosage compensation Dosage compensation is the process by which organisms equalize the expression of genes between members of different biological sexes. Across species, different sexes are often characterized by different types and numbers of sex chromosomes. In order ...
. *In ''
D. melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...
'', condensin II subunits contribute to the dissolution of polytene chromosomes and the formation of
chromosome territories In cell biology, chromosome territories are regions of the nucleus preferentially occupied by particular chromosomes. Interphase chromosomes are long DNA strands that are extensively folded, and are often described as appearing like a bowl of ...
in ovarian nurse cells. Evidence is available that they negatively regulate transvection in diploid cells. It has also been reported that condensin I components are required to ensure correct gene expression in neurons following cell-cycle exit. *In ''
A. thaliana ''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small flowering plant native to Eurasia and Africa. ''A. thaliana'' is considered a weed; it is found along the shoulders of roads and in disturbed land. A winter a ...
'', condensin II is essential for tolerance of excess boron stress, possibly by alleviating DNA damage. *In mammalian cells, it is likely that condensin II is involved in the regulation of interphase chromosome architecture and function. For instance, in human cells, condensin II participates in the initiation of sister chromatid resolution during S phase, long time before mitotic prophase when sister chromatids become cytologically visible. *In mouse
interphase Interphase is the portion of the cell cycle that is not accompanied by visible changes under the microscope, and includes the G1, S and G2 phases. During interphase, the cell grows (G1), replicates its DNA (S) and prepares for mitosis (G2). A c ...
nuclei, pericentromeric heterochromatin on different chromosomes associates with each other, forming a large structure known as chromocenters. Cells deficient in condensin II, but not in condensin I, display hyperclustering of chromocenters, indicating that condensin II has a specific role in suppressing chromocenter clustering. *Whilst early studies suggested the possibility that condensins may directly participate in regulating gene expression, some recent studies argue against this hypothesis. *
Mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...
s of the fission yeast ''
Schizosaccharomyces pombe ''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measur ...
'' were obtained that had a temperature sensitive and/or
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 d ...
sensitive phenotype.Xu X, Nakazawa N, Yanagida M. Condensin HEAT subunits required for DNA repair, kinetochore/centromere function and ploidy maintenance in fission yeast. PLoS One. 2015 Mar 12;10(3):e0119347. doi: 10.1371/journal.pone.0119347. PMID: 25764183; PMCID: PMC4357468 Some of these mutants were defective in the HEAT subunits of condensin indicating that the HEAT subunits are required for
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 da ...
.


Posttranslational modifications

Condensin subunits are subjected to various posttranslational modifications in a cell cycle-dependent manner. Among them, the best-studied example is
phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
. For instance,
Cdk1 Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in t ...
(Cyclin-dependent kinase 1) activates condensin I, whereas CK2 (Casein kinase 2) negatively regulate its activity. It has been reported that, in ''
D. melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...
'', the CAP-H2 subunit of condensin II is degraded through the action of SCFSlimb
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 ubiquit ...
.


Relevance to diseases

It was demonstrated that MCPH1, one of the proteins responsible for human primary
microcephaly Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...
, has the ability to negatively regulate condensin II. In ''mcph1'' patient cells, condensin II (but not condensin I) is hyperactivated, leading to premature chromosome condensation in G2 phase (i.e., before entering mitosis). There is no evidence, however, that misregulation of condensin II is directly related to the etiology of ''mcph1'' microcephaly. More recently, it has been reported that hypomorphic mutations in condensin I or II subunits cause microcephaly in humans. In mice, hypomorphic mutations in condensin II subunits cause specific defects in
T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
development, leading to
T cell lymphoma T-cell lymphoma is a rare form of cancerous lymphoma affecting T-cells. Lymphoma arises mainly from the uncontrolled proliferation of T-cells and can become cancerous. T-cell lymphoma is categorized under Non-Hodgkin lymphoma (NHL) and represents ...
. It is interesting to note that cell types with specialized cell division modes, such as
neural stem cells Neural stem cells (NSCs) are self-renewing, multipotent cells that firstly generate the radial glial progenitor cells that generate the neurons and glia of the nervous system of all animals during embryonic development. Some neural progenitor ste ...
and
T cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ...
, are particularly susceptible to mutations in condensin subunits.


Evolutionary implications

Prokaryotes have primitive types of condensins, indicating that the evolutionary origin of condensins precede that of histones. The fact that condensins I and II are widely conserved among extant eukaryotic species strongly implicates that the last eukaryotic common ancestor ( LECA) had both complexes. It is therefore reasonable to speculate that some species such as fungi have lost condensin II during
evolution Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
. Then why do many eukaryotes have two different condensin complexes? As discussed above, the relative contribution of condensins I and II to mitosis varies among different organisms. They play equally important roles in mammalian mitosis, whereas condensin I has a predominant role over condensin II in many other species. In those species, condensin II might have been adapted for various non-essential functions other than mitosis. Although there is no apparent relationship between the occurrence of condensin II and the size of genomes, it seems that the functional contribution of condensin II becomes big as the genome size increases. A recent, comprehensive Hi-C study argues from an evolutionary point of view that condensin II acts as a determinant that converts post-mitotic Rabl configurations into interphase chromosome territories. The relative contribution of the two condensin complexes to mitotic chromosome architecture also change during development, making an impact on the morphology of mitotic chromosomes. Thus, the balancing act of condensins I and II is apparently fine-tuned in both evolution and development.


Relatives

Eukaryotic cells have two additional classes of
SMC protein SMC complexes represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes. Classification Eukaryotic SMCs Eukaryotes have at l ...
complexes.
Cohesin Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping. Cohesin is formed of SMC3, SMC1, SCC1 and SCC3 ( SA1 or SA2 in humans). Cohesin holds sister chromatids together after DNA rep ...
contains SMC1 and SMC3 and is involved in sister chromatid cohesion. The SMC5/6 complex contains SMC5 and SMC6 and is implicated in recombinational repair.


See also

*
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 ...
* nucleoid * mitosis *
meiosis Meiosis (; , since it is a reductional division) 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 resu ...
*
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 sub ...
*
cohesin Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping. Cohesin is formed of SMC3, SMC1, SCC1 and SCC3 ( SA1 or SA2 in humans). Cohesin holds sister chromatids together after DNA rep ...
*
SMC protein SMC complexes represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes. Classification Eukaryotic SMCs Eukaryotes have at l ...
* ATPase *
HEAT repeat A HEAT repeat is a protein tandem repeat structural motif composed of two alpha helices linked by a short loop. HEAT repeats can form alpha solenoids, a type of solenoid protein domain found in a number of cytoplasmic proteins. The name "HEAT" ...
*
Topoisomerase II Type II topoisomerases are topoisomerases that cut both strands of the DNA helix simultaneously in order to manage DNA tangles and supercoils. They use the hydrolysis of ATP, unlike Type I topoisomerase. In this process, these enzymes change th ...
*
DNA supercoil DNA supercoiling refers to the amount of twist in a particular DNA strand, which determines the amount of strain on it. A given strand may be "positively supercoiled" or "negatively supercoiled" (more or less tightly wound). The amount of a st ...


References


External links

* {{Nucleus Cell cycle Mitosis Protein complexes