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The chromosomal DNA is stacked with help of cohesin and condensin protein in which particular manner? Can cohesin be said to form kinetochore? How would they vary exactly? The terms are so narrowly windowed that they squeeze my brain through… !!! thank you for your kind help ^_^
Condensin I: present in cytoplasm during interphase, has access to chromosomes after prophase. Contributes to condensed chromosome assembly during prometaphase and metaphase .
Condensin II: present in nucleus during interphase, involved in chromosome condensation. Contributes to condensed chromosome assembly during prometaphase and metaphase .
It keeps sister chromatids connected with each other during metaphase and ensures that each sister chromatid segregates to opposite poles. "It facilitates spindle attachment onto chromosomes. It facilitates DNA repair by recombination." 
- Wikipedia contributors, "Condensin," Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/w/index.php?title=Condensin&oldid=606814199 (accessed July 29, 2014).
- Wikipedia contributors, "Cohesin," Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/w/index.php?title=Cohesin&oldid=617481362 (accessed July 29, 2014).
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 replication until anaphase when removal of cohesin leads to separation of sister chromatids. The complex forms a ring-like structure and it is believed that sister chromatids are held together by entrapment inside the cohesin ring. Cohesin is a member of the SMC family of protein complexes which includes Condensin, MukBEF and SMC-ScpAB.
Cohesin was separately discovered in budding yeast by Douglas Koshland  and Kim Nasmyth. 
Two related protein complexes, cohesin and condensin, are essential for separating identical copies of the genome into daughter cells during cell division. Cohesin glues replicated sister chromatids together until they split at anaphase, whereas condensin reorganizes chromosomes into their highly compact mitotic structure. Unexpectedly, mutations in the subunits of these complexes have been uncovered in genetic screens that target completely different processes. Exciting new evidence is emerging that cohesin and condensin influence crucial processes during interphase, and unforeseen aspects of mitosis. Each complex can perform several roles, and individual subunits can associate with different sets of proteins to achieve diverse functions, including the regulation of gene expression, DNA repair, cell-cycle checkpoints and centromere organization.
Sex Determination in Vertebrates
Tasman Daish , Frank Grützner , in Current Topics in Developmental Biology , 2019
6 A role for SMCs in sex chromosome organization: Cohesins are key players in the regulation of meiotic pairing dynamics
Cohesins and their close functional and structural relative, the condensins , are multi-component molecules with diverse functions in genome regulation including mitotic and meiotic division, DNA repair, transcriptional control, and chromosome condensation. Mutations affecting cohesins result in reproductive and fertility deficits and cancer ( Litwin & Wysocki, 2018 Rankin, 2015 Remeseiro & Losada, 2013 ). The primary and best characterized roles for cohesin are homolog and sister chromatid tethering during mitotic and meiotic cell divisions. In humans and mice, the meiotic-specific cohesin complex assembles in a tri-partite configuration composed of the structural maintenance of chromosomes (SCC) proteins SMC1β and SMC3, the bridging or linker α-kleisin subunit Rad21, which is also bound by the stromal antigen protein STAG3. This structure forms a ring in which the DNA strands of meiotic homologs and sister chromatids are held until their separations in Meiosis I and II, respectively. Consequently, these proteins are essential for successful gametogenesis ( Biswas et al., 2016 Hopkins et al., 2014 Ward, Hopkins, McKay, Murray, & Jordan, 2016 ). The cohesins and especially SMC3 are integral components of the SC where they participate in chromosome condensation and pairing. Recent evidence has implicated a possible role in sex chromosome specific regulation in the platypus ( Casey et al., 2017 ). Another meiosis specific cohesin variant, RAD21L, is associated with the sex body in mouse and there are functional links between cohesin components, the nucleolus, and heterochromatin formation. The observed massive accumulation of SMC3 and STAG3 specifically to the unpaired regions of the platypus sex chromosome chain through pachytene is an intriguing observation ( Casey et al., 2017 Herran et al., 2011 Ishiguro, Kim, Fujiyama-Nakamura, Kato, & Watanabe, 2011 ). The marked accumulation of these two cohesin components specifically to meiotic sex chromosomes has not previously been observed in any species, and the fact that it is restricted to unpaired DNA and is not associated with the multiple PARs, implicates a role specific to the 10 sex chromosomes. Furthermore, accumulation occurs concomitant with the transient contraction and coalescing of the 10 elements into a heterochromatic paranucleolar mass ( Fig. 1 Lower panel). These observations require further investigation, including the determination of the cohesin status of the equalized ZW in pachytene chicken oocytes, to identify the degree of conservation of strategies utilized to manage heteromorphic sex chromosomes.
Cohesin and condensin are essential components of the chromatin spring. Using model convolution on simulated geometries of cohesin and condensin, we determined their fine structures within pericentric chromatin. Cohesin is best matched by a random distribution of fluorophores populating a barrel 500 nm in diameter and 550 nm in length and a single complex ∼40 nm thick. Condensin fluorescence is best matched by clustered fluorophores occupying a 350-nm hollow cylinder proximal to the interpolar spindle microtubules. Understanding the differences between cohesin and condensin distributions in the pericentromere allow us to gain insight into their functions in the chromatin spring.
Pericentric cohesin has been proposed to be organized into a barrel distribution around the spindle microtubules (Yeh et al., 2008). This is consistent with the cylinder-like organization of spindle microtubules seen with EM tomography and the distribution of pericentric chromatin labeled with LacO/LacI-GFP (Winey et al., 1995 Gardner et al., 2008 Anderson et al., 2009 Stephens et al., 2011 Haase et al., 2012). We show here that experimental pericentric cohesin fluorescence from various angles of acquisition is faithfully recapitulated by simulated images of a hollow cylinder/barrel (Figure 2). Cohesin's homogeneous distribution is best matched by single, randomly distributed fluorophores (Figure 4). The barrel is continuous only in the sense that the fluorescence distribution of individual molecules overlaps as a consequence of the objective PSF. We can rule out multiple layers within the barrel (or multiple concentric barrels) based on the simulations that indicate the thickness of the barrel is comparable to a single cohesin ring (Figure 2D and Table 2). Our modeling does not address whether the molecules exist as single or multiple complexes (Haering and Jessberger, 2012). Model convolution data are consistent with cohesin dispersed throughout a barrel geometry surrounding the central spindle.
The distribution of condensin differs from cohesin in that it is neither bilobed nor homogeneous. By measuring the number of molecules, we know that the differences are not due to a disparity in the number of molecules, as both have ∼240 total in the total pericentric chromatin of 16 sister chromatids. To mimic cell-to-cell heterogeneity, we reduced the number of unique positions the fluorophores occupy in the cylinder via clustering and randomized fluorophore positions from image to image. The random distribution of clusters (eight or 16 fluorophores per cluster) in simulations best matches condensin's heterogeneous axial fluorescence with approximately equal frequency of a focus, two foci, or uniform signal (Figure 3). Even in mcm21Δ cells with an increased interkinetochore length, the frequency of different fluorescent signals is accurately matched by simulations of clustering (Figure S1B). Compiling experimental condensin images from a population of aligned spindles revealed no preferred position within the pericentromere. The ensemble fluorescence was evenly distributed between kinetochores (Stephens et al., 2011). Taken together, the data suggest that condensin clusters are randomly distributed in the pericentromere and along the spindle axis.
Condensin clusters likely form rosettes in the pericentromere to resist tension via homotypic interactions (Figure 6). The idea of multiple loops stemming from clustered condensin has been proposed as a mechanism for chromatin compaction (Vas et al., 2007 Hirano, 2012). Biochemical and theoretical studies suggest condensins work cooperatively (Melby et al., 1998 Strick et al., 2004 Alipour and Marko, 2012). Our data support a model in which multiple condensins (8–16) cluster to compact the pericentromere along the spindle axis (Figure 3). Compaction likely occurs through condensin gathering of distal regions of DNA to produce chiral loops (Kimura and Hirano, 1997 Yoshimura et al., 2002 Strick et al., 2004 Hirano, 2006 Figure 6). Condensin has been shown to bind to and cluster at tRNA genes, as well as at other sites occupied by transcription factor TFIIIC (D'Ambrosio et al., 2008 Haeusler et al., 2008 Iwasaki et al., 2010), providing a mechanism to cluster pericentromere loci. Sir2 aids in the recruitment of condensin to tRNA sites (Li et al., 2013), and upon Sir2 depletion, condensin may lose affinity for these sites, which may explain why condensin becomes displaced from the spindle axis in sir2Δ mutants (Figure 5). Condensin binding is negatively correlated with transcription activity in the rDNA locus as well as the centromere (Johzuka and Horiuchi, 2007, 2009 Iwasaki et al., 2010). An alternative but not mutually exclusive mechanism for condensin displacement in sir2Δ cells is that Sir2 functions to hypoacetylate centromere and pericentromere regions (Choy et al., 2011, 2012) to promote transcription silencing in order to ensure proper condensin recruitment/binding. A chromatin spring composed of loops is consistent with mathematical models that recapitulate experimental spindle behavior upon perturbation of the chromatin spring via pericentric cohesin or condensin depletion (Stephens et al., 2013).
FIGURE 6: Model of cohesin and condensin in the pericentromere. (A) Condensin (light blue) is localized along the spindle axis in clusters, where it forms rosette-like loops through multiple condensin working cooperatively. Cohesin (dark blue) is localized radially, where it promotes looping to resist outward pulling forces from spindle microtubules. Cohesin is shown as two possible configurations: a single complex (left) or two complexes (right see review in Haering and Jessberger, 2012). (B) Diagram of the intercentromere region. While condensin can span the length between sister centromere clusters, cohesin is displaced from the centromere cluster by ∼125 nm.
Cohesin is randomly distributed on radially dispersed pericentromere loops. The broad distribution of centromere-linked LacO arrays provides an independent estimate of the size of the cohesin barrel. In 92% of cells, pericentric LacO arrays are confined within a 530-nm diameter surrounding the spindle (see Figure 4C, III). On treatment of cells with a low dose of benomyl, both pericentric chromatin radial position and the width of cohesin barrel increase (Haase et al., 2012). The expansion of pericentric chromatin depends upon Bub1-dependent phosphorylation of H2AS121A (Haase et al., 2012). Thus it is the chromatin that dictates the dimensions of the cohesin barrel. The aggregate pericentric chromatin (32 × 50 kb = 1.6 Mbp) in mitosis is comparable in size to the entire Escherichia coli nucleoid (∼4 Mbp). Because the pericentromere is confined to a similar volume, it is likely to exhibit features of confinement displayed by the bacterial nucleoid and subject to entropic polymer repulsion that facilitates chromosome segregation (Jun and Mulder, 2006 Fisher et al., 2013). Cohesin plays a critical function in confining the chromatin to this radial position (depicted in Figure 6 Stephens et al., 2011). Cohesin embracing radial loops of different pericentromeres would generate a cross-linked network (Stephens et al., 2013), which would further confine the pericentric chromatin. We therefore propose that cohesin's molecular functions in entrapment and compaction (Gruber et al., 2003 Haering et al., 2008 Sun et al., 2013) lead to confinement and cross-linking within the chromatin spring.
Interestingly cohesin's distribution does not span the entire pericentromere from kinetochore to kinetochore and instead is ∼125 nm away from either centromere cluster. The eviction of cohesin from the centromere may be necessary for proper orientation. Having cohesion at the centromere promotes monorientation of sister centromeres, whereas cohesion in the pericentromere promotes biorientation (Sakuno and Watanabe, 2009). A similar but alternative idea is that condensin could be displacing cohesin to aid in centromere resolution, as has been reported in Caenorhabditis elegans (Moore et al., 2005).
Model convolution provides a noninvasive method to determine the fine structure and distribution of cohesin and condensin in the mitotic segregation apparatus. Computer simulations of different fluorophore geometries and distributions were convolved with the PSF to directly assess experimental images. The axial position and clustering of condensin versus the radial position and dispersion of cohesin leads to insights into the arrangement of the chromatin spring. A rosette of pericentromere loops is compacted and confined in a geometry that distributes tension generated at multiple microtubule attachment sites throughout the chromatin network.
Cohesin and condensin are the two most widely studied nonhistone protein complexes with important roles in mitotic chromosome structure and behavior. The present study serves to highlight that even though these two complexes are superficially similar (e.g., both are built around SMC protein heterodimers), the role played by ATP in the function of the two complexes is apparently distinct.
Mechanistic Differences Between Cohesin and Condensin ATPase Function
Our study shows ATP binding and hydrolysis by SMC2 are not required for the assembly of the condensin holocomplex. A separate study using baculovirus purified condensin I also found that ATPase mutations in either SMC2 or SMC4 failed to affect the formation of the holocomplex in vitro (Onn et al., 2007). In contrast, ATP binding in the cohesin subunit SMC1 but not SMC3 is essential for interactions with Scc1 and therefore for assembly of the cohesin complex (Arumugam et al., 2003 Weitzer et al., 2003).
We also report the first functional analysis of the conserved Q-loop found in all SMC proteins. This motif has been proposed to bind water and magnesium and to undergo a conformational change upon substrate binding (Hopfner et al., 2000 Hopfner and Tainer, 2003). It has been suggested that this acts as a “lever arm” to transduce ATP binding and hydrolysis into physical action by the SMC protein (Hopfner and Tainer, 2003). We found that SMC2 Q-loop mutant Q147L has no effect on the formation of the condensin holocomplex, but abolished its association with chromosomes. It remains to be determined whether this Q-loop mutant has impaired ATPase function or acts downstream of ATP to disrupt a conformational change required for condensin loading.
ATP-binding, but not hydrolysis is required for the association of condensin with mitotic chromosomes in vivo. Despite the fact that SMC2 mutants D1113A and K38I, which are predicted to block ATP binding, are able to participate in formation of the condensin complex, complexes containing these mutations failed to associate with chromosomes. In contrast, the SMC2-E1114Q mutant, which is predicted to slow the rate of ATP hydrolysis, bound to chromosomes at levels comparable with wild type. The SMC2-S1086R mutant bound chromosomes less well, possibly reflecting its ability to bind, but not to hydrolyze, ATP. These results are consistent with those of an in vitro study of Bacillus subtillus SMC homodimers, in which transition state mutants (analogous to SMC2-E1114Q) allowed detectible DNA binding (Hirano and Hirano, 2004). In contrast, cohesin complexes with the analogous ATP hydrolysis mutation in either SMC1 or SMC3 fail to load onto chromatin (Arumugam et al., 2003).
Our in vivo studies of condensin function are consistent with recent in vitro studies from the Hirano laboratory, which showed that purified SMC2 undergoes a conformational shift in the presence of ATP, leading to the suggestion that ATP binding might open the hinge region (Onn et al., 2007). Recent studies of cohesin have shown that loading of the complex onto chromatin is caused by transient opening of the hinge domain, and it was hypothesized that this conformational change could be the result of either ATP binding or hydrolysis (Gruber et al., 2006). Thus, it seems that ATPase activity within the head domain could relay the conformational changes required to open the hinge region for SMC proteins (Figure 7).
Figure 7. Hypothetical working model for condensin binding to chromosomes showing ATP binding producing a conformational change that allows DNA entry into an altered hinge region. Mutations blocking ATP binding (K38I, D1113A) or allosteric change (Q147L) inhibit condensin loading onto chromosomes. ATP hydrolysis results in the disengagement of the SMC2 and SMC4 head domains allowing intermolecular multermerization between condensins and formation of higher order structures. Mutations affecting ATP hydrolysis (S1086R, E1114Q) allow condensin to associate with chromatin but may affect the multermerization properties of the complex. In contrast to cohesin, condensin remains associated with chromatin after breakage of a SMC subunit most likely due to strong intermolecular interactions between the coiled-coil regions of SMC2 and SMC4.
Regardless of the mechanism, cells expressing the mutated ATPase domains in SMC2 are unable to form functional condensin complex. Although the results reported here represent a first attempt using a genetic approach to understanding the role of condensin ATPase function in vivo, further work is required for a definitive characterization of the ATPase cycle in purified condensin.
Cleavage of SMC2 Does Not Alter Condensin Association or Binding to Chromosomes in Vitro
One key to understanding the function of condensin is to ascertain whether the complex forms a closed ring structure and traps DNA in a manner analogous to that proposed for cohesin (Ivanov and Nasmyth, 2005). Electron microscopy studies reveal that the cohesin arms seem to form an open loop, and they are thus topologically in a position to encircle DNA, whereas condensin predominately forms a “lollipop” like structure with the arms tightly apposed to one another (Anderson et al., 2002). Our observations that the condensin complex remains largely intact despite the cleavage of SMC2 are consistent with the notion that condensin arms are apposed in a lollipop structure. Our results thus support the notion that condensin acts via a mechanism distinct from cohesin.
By analogy to experiments with the cohesin subunit SMC3 (Gruber et al., 2003), cleavage sites were chosen that would break SMC2 in regions of lowered propensity for coiled-coil formation and therefore would not interfere with the structure of the complex. However, we cannot exclude the possibility that interactions between SMC2 helices (or with SMC4) in the coiled-coil might be retained even after protease cleavage. After in vitro cleavage of SMC2 by PreScission protease, a significant portion of the middle hinge/dimerization region could be substantially solubilized (Figure 5B), consistent with cleavage rather than simply “nicking” the SMC2 coiled-coil, whereas the C and N domains remain tightly associated (Figure 5, C and D). In the previous study of cohesin, when cleavable SMC3 was expressed and cleaved in vitro on beads, approximately half of the dimerization domain was released, suggesting comparable cleavage of SMC proteins between the two systems (Gruber et al., 2003). However, given the predicted lollipop conformation for the condensin holocomplex, we cannot say whether cleavages within the SMC2 coiled-coil open the complex entirely when the complex is bound to chromosomes.
Cleavage of SMC3 releases the cohesin complex from chromatin and can initiate the onset of sister chromatid separation, even though it does not alter the interactions between SMC3, SMC1, or Scc1 (Gruber et al., 2003). When SMC2 in purified condensin is cleaved by PreScission protease, the complex seems to remain intact without any significant loss of either the condensin I or II non-SMC subunits. This was true even under stringent tandem purification conditions with multiple washes in a buffer that included the ionic detergent deoxycholate. Furthermore, when isolated chromosomes were treated with PreScission protease, SMC2 remained concentrated along the chromatid axes despite being quantitatively cleaved. Therefore, condensin complex stability and association with mitotic chromosomes is not dependent upon the integrity of the SMC2 heterodimer. In contrast, the chromosome association of DNA topoisomerase IIα was specifically altered after SMC2 cleavage. This demonstrates that the PreScission cleavage of SMC2 did indeed alter condensin structure or function, and it suggests a close association of Topo IIα with the condensin complex in chromosomes.
Cleavage of the SMC2 coils might be expected to release the complex from chromatin if condensin were to bind DNA by an “embrace” model as proposed for cohesin. However, the failure to release the complex from chromosomes after SMC2 scission suggests that chromosome association by condensin may not solely require topological closure of the complex. Thus, the SMC arms of condensin might transmit conformational changes that enable loading or unloading of the complex.
To date the only direct visualization of condensin associated with DNA was provided by atomic force microscopy of the purified fission yeast complex (Yoshimura et al., 2002). The work showed condensin as sitting on DNA with its hinge but not topologically embracing DNA, and in some instances with the heads bending down to the DNA. It is possible, however, these images represent condensin trapped in a preloading state because of the limited biochemical activity of the preparation or absence of loading factors (Uhlmann and Hopfner, 2006).
The way in which condensin interacts with DNA therefore remains an open question. Our in vivo data have demonstrated the importance of the ATPase cycle of condensin in regulating this process. Together, our work and the work performed by others have served to highlight a SMC paradox in which remarkably similar proteins that form highly analogous complexes seem to function by distinct mechanisms.
International Review of Cell and Molecular Biology
2.3 Chromatin State
In addition to DNA amount, chromatin compaction is another feature that potentially impacts nuclear size and morphology. The large number of proteins known to interact with and modify chromatin complicates this question ( Kustatscher et al., 2014 ), although roles for condensins and histones have emerged. For example, increasing condensin II-mediated chromatin compaction in Drosophila caused distortion of NE morphology ( Buster et al., 2013 ). An analysis of 160 eukaryotic genomes showed that as genome size increased during evolution, the amino terminus of histone H2A has acquired arginine residues that confer increased chromatin compaction. Addition of arginine residues to the yeast H2A resulted in increased chromatin compaction and reduced nuclear volume, while mutating arginine residues in human H2A led to chromatin decompaction and increased nuclear size ( Macadangdang et al., 2014 ).
It is worth noting that chromatin compaction might also indirectly impact nuclear size. Yeast cells increase compaction of long chromosome arms during mitosis to ensure complete chromosome segregation ( Neurohr et al., 2011 ), whereas Drosophila cells transiently elongate during anaphase ( Kotadia et al., 2012 ). In both instances, this might affect nuclear size in the subsequent interphase. Histone H3 methylation status has been shown to dictate chromatin regions that associate with the nuclear lamina, so called lamina-associated domains (LADs) ( Harr et al., 2015 ), and certain long noncoding RNAs regulate histone methylation ( Wang et al., 2011b ). Chromatin organization might, in turn, affect nuclear size. Also see Sections 3.1, 3.2, 3.4, 3.7, 3.8, 4.1 , and 4.3 .
S1 Fig. Condensin I affects cohesin localization at entry into meiosis.
(A) Immunofluorescence images of COH-3/4 and REC-8 staining in the mitotic tip (MT) and transition zone (TZ) of wild type and dpy-28 mutant male germlines treated with control vector or wapl-1 RNAi. COH-3/4 is not detectable in the MT, and first appears on chromosomes in the TZ. Staining intensity is reduced in the TZ in dpy-28 mutants. REC-8 is nucleoplasmic in the MT and appears as long threads on chromosomes in the TZ. In dpy-28 mutants, localization patterns are unchanged in the MT, but staining intensity is reduced in TZ. wapl-1 RNAi restores cohesin staining intensity to near wild type levels. Scale bar, 5 μm (B) Metaphase I stage in wild type and dpy-28 mutant males. REC-8 and COH-3/4 are shown in green. Cohesin staining intensities and localization appear similar in wild type and mutant, with COH-3/4 enriched between paired homologs (arrows). Scale bar, 1 μm.
S2 Fig. Cohesin and SC localization in condensin I depletion and condensin II mutants.
(A) Immunofluorescence images of REC-8 and COH-3/4 staining in early pachytene (EP), and late pachytene (LP) nuclei of rrf-1 hermaphrodites treated with control vector or capg-1 RNAi. Chromosomal association of REC-8 and COH3/4 is reduced after CAPG-1 depletion. (B) Control experiment showing lack of COH-3/4 staining in coh-4 coh-3 mutants and lack of REC-8 staining in rec-8 mutants. (C) Images of single bivalents (paired homologs) at diakinesis in rrf-1 hermaphrodites. COH-3/4 (green) is enriched at the short arm of bivalents (between homologs, arrows). and REC-8 (green) is initially visible on both arms, but eventually is more prominent on the long arm (between sisters, arrows). Staining patterns are comparable in control and in capg-1(RNAi). (D) Immunofluorescence images of gonads from control and capg-2 RNAi-treated worms stained with antibodies specific for SYP-1 (red) and COH-3/4 (green) on the left and HTP-3 (red) and REC-8 (green) on the right. DNA is stained with DAPI (blue). Depletion of CAPG-2 did not perturb cohesin or SC localization. Scale bars, 5 μm in A, B, and D, and 1 μm in C.
S3 Fig. Double strand DNA break repair and apoptosis in condensin I-depleted germlines.
(A) Immunofluorescence images of wild type male and dpy-28(tm3535) male gonads stained with antibodies specific to double strand DNA break marker RAD-51. Scale bar, 5 μm. (B) Quantification of RAD-51 foci in different zones of the male germline. In dpy-28 mutants, the number of foci increase, particularly in early pachytene (EP) and mid pachytene (MP). By late pachytene, breaks are resolved in both genotypes. Numbers of nuclei analyzed and p values are shown in S1 Table. (C) Quantification of apoptotic nuclei in hermaphrodites expressing the apoptosis marker CED-1::GFP, treated with control vector or capg-1 RNAi. Total numbers of apoptotic bodies per gonad arm are shown. Germline apoptosis increases after capg-1 RNAi. *** indicates statistical significance (p<0.001) by two-tailed unpaired t-test.
S4 Fig. SYP-1 aggregates are observed in htp-3 mutants.
Immunofluorescence images in wild type and htp-3 mutant hermaphrodite gonads stained with SYP-1 antibodies. SYP-1 forms long tracks along chromosomes in wild type worms, but it is present in aggregates in htp-3 mutants.
S1 Table. Numerical and statistical data.
Numerical data underlying graphs and summary statistics.
Structural Basis for Dimer Formation of Human Condensin Structural Maintenance of Chromosome Proteins and Its Implications for Single-stranded DNA Recognition
Eukaryotic structural maintenance of chromosome proteins (SMC) are major components of cohesin and condensins that regulate chromosome structure and dynamics during cell cycle. We here determine the crystal structure of human condensin SMC hinge heterodimer with
30 residues of coiled coils. The structure, in conjunction with the hydrogen exchange mass spectrometry analyses, revealed the structural basis for the specific heterodimer formation of eukaryotic SMC and that the coiled coils from two different hinges protrude in the same direction, providing a unique binding surface conducive for binding to single-stranded DNA. The characteristic hydrogen exchange profiles of peptides constituted regions especially across the hinge-hinge dimerization interface, further suggesting the structural alterations upon single-stranded DNA binding and the presence of a half-opened state of hinge heterodimer. This structural change potentially relates to the DNA loading mechanism of SMC, in which the hinge domain functions as an entrance gate as previously proposed for cohesin. Our results, however, indicated that this is not the case for condensins based on the fact that the coiled coils are still interacting with each other, even when DNA binding induces structural changes in the hinge region, suggesting the functional differences of SMC hinge domain between condensins and cohesin in DNA recognition.
Keywords: analytical ultracentrifugation chromatin structure chromosomes crystal structure hydrogen exchange mass spectrometry isothermal titration calorimetry (ITC) protein-DNA interaction.
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Chapter 10: How Cells Divide
Chromosome number vary among different species- human have 46 chromosomes, consisting of 23 nearly identical pairs.
Every 200 nucleotides, the DNA duplex is coiled around a core of 8 HISTONE PROTEINS- positively charged proteins due to an abundance of the amino acids arginine and lysine.
The complex of DNA and histone proteins are called the NUCLEOSOME.
The DNA wrapped in nucleosomes is further coiled into an even more compact structure called the SOLENOID- the 30 nm fiber. This is the usual state of nondividing chromatin.
After replication, each chromosome is composed of two identical DNA molecules held together by a complex of proteins called COHESINS (complex of proteins holding replicated chromosomes together).
1. G1 (gap phase 1) the primary growth phase of the cell. The term gap phase refers to its filling the gap between cytokinesis and DNA synthesis. For most cells, this is the longest phase.
2. S (synthesis) is the phase in which the cell synthesizes a replica of the genome. (DNA replication)
3. G2 (gap phase 2) is the second growth phase, and preparation for separation of the newly replicated genome. This phase fills the gap between DNA synthesis and the beginning of mitosis. During this phase microtubules begin to reorganize to form a spindle. Chromosomes condense.
* G1, S, and G2 together constitute INTERPHASE, the portion of the cell cycle between divisions.
4. MITOSIS is the phase of the cell cycle in which the spindle apparatus assembles, binds to the chromosomes, and moves the sister chromatids apart. Mitosis is the essential step in separation of the two daughter genomes. It is traditionally subdivided into five stages: prophase, prometaphase, metaphase, anaphase, and telophase.
5. CYTOKINESIS is the phase of the cell cycle when the cytoplasm divides, creating two daughter cells. In animal cells, the microtubule spindle helps position a contracting ring of actin that constricts like a drawstring to pinch the cell in two. In cells with a cell wall, such as plant cells, a plate forms between the dividing cells.
* Mitosis and cytokinesis together are usually referred to collectively as M phase, to distinguish the dividing phase from interphase.