Chromosomes during Cell Division


In mitosis, duplicated deoxyribonucleic acid (DNA) goes through a condensation/decondensation cycle. This is followed by nuclear envelope dissolution, mitotic spindle assembly, migration of the sister chromatid pairs to the metaphase plate, division and segregation of identical sets of chromosomes into daughter nuclei and nuclear envelope reformation. This process results in the formation of two genetically identical daughter cells. Dynamic structural changes and the mitotic spindle‚Äźmediated movement are two major features that occur to chromosomes during cell division. Both features are well coordinated with temporal progression of mitosis consisting of five distinct stages (prophase, prometaphase, metaphase, anaphase and telophase), which are regulated by checkpoint mechanisms to maintain genomic integrity. Defects in chromosome segregation are linked to cancer and several genetic diseases. Some enzymes involved in chromosome regulation during cell division have become attractive drug targets.

Key Concepts:

  • Mitosis is the process of cell division that results in two genetically identical daughter cells.

  • Mitosis consists of five stages: prophase, prometaphase, metaphase, anaphase and telophase.

  • Chromosomes are classified according to centromere location as metacentric, submetacentric or acrocentric.

  • Chromosome movement in mitosis is a dynamic process controlled by microtubule dynamics and microtubule‚Äźassociated motor or nonmotor proteins.

  • Sister chromatid cohesion is established in S phase and is dissolved in two steps in vertebrate mitoses.

  • A kinetochore complex forms at the centromere in mitosis to allow microtubule capture.

  • Mitosis is a coordinated process regulated by checkpoint mechanisms to maintain genomic integrity.

  • Chromosomal missegregation results in cell death or aneuploidy.

Keywords: mitosis; chromosomes; spindle assembly checkpoint; kinetochore; centromere; centrosome; condensation; cohesion; kinesin

Figure 1.

Stages of mitosis with fluorescence in situ hybridisation (FISH) to show centromere localisation of human chromosomes. (a) Prophase nucleus showing the ‘worm‐like’ prophase chromosomes. (b) Prometaphase, side view with all centromeres stained green (anti‐CENP‐A fluorescence) and the mitotic spindle stained red (anti‐tubulin fluorescence). (c) Prometaphase rosette, end‐on view showing the chromosomes arranged in a tight mitotic ring. (d) Metaphase, end‐on view of the metaphase mitotic ring showing some separation of the chromosomal arms of the sister chromatid pairs. (e) Metaphase, side view showing almost perfect alignment of the FISH‐localised centromeres at the metaphase plate. (f, g) Early and late anaphases showing symmetrical positions of divided, FISH‐localised homologous centromeres. (h) Telophase pair with symmetrical positions of homologous centromeres in the daughter chromosomal masses. (a), (d), (e), (f) and (g) show centromere FISH of chromosomes 11 (green) and 17 (red); (c) and (h) show centromeres of chromosome X (green), 17 (red) and 7 (red) in male cells. The pre‐anaphase FISH localisations (a–e) show undivided centromeres. Bar, 20 μm. Reproduced and modified from Allison and Nestor by copyright permission of The Rockefeller University Press.

Figure 2.

Submetacentric and acrocentric metaphase chromosomes. The sister chromatids of both chromosomes are joined at the centromere. Kinetochores are built on centromeric chromatin. The ends of the sister chromatids are capped with telomeres, and alternating R and G bands are depicted as stripes between the centromere and telomeres.

Figure 3.

The cohesin complex and cell cycle–dependent regulation of chromosome cohesion. (a) Model for the architecture of the cohesin complex on chromatin. In somatic vertebrate cells, the cohesin core complex consists of Smc1, Smc3, Scc1 and either SA1 or SA2. Association of Wapl with the core complex depends on Scc1 and SA1 (indicated by arrows), and there is evidence that Wapl directly interacts with Pds5 (dashed line) (Kueng et al., ). How sororin interacts with cohesin is unknown. According to the ‘ring’ model, cohesin mediates sister chromatid cohesion by topological embrace, and it has been suggested that the tripartite ring formed by Smc1, Smc3 and Scc1 could encircle two 10‐nm chromatin fibres. (b) Regulation of sister chromatid cohesion during the vertebrate cell cycle. Loading of cohesin onto chromatin occurs during telophase and G1 and requires the cohesin loading factors Scc2 and Scc4. In Xenopus egg extracts, cohesin loading also depends on the assembly of pre‐replication complexes (pre‐RCs) on chromatin. During S phase, cohesion between sister chromatids is established, and this process may depend on sororin, ESCO1 and ESCO2. During prophase, the bulk of cohesin dissociates from chromatin, and this removal is regulated by Plk1, Aurora B kinase, condensin I and Wapl. Cohesin at centromeres is protected by Sgo1 and PP2A. At the metaphase‐to‐anaphase transition, separase is activated by the APC/C and cleaves centromeric cohesin as well as residual cohesin on chromosome arms, enabling sister chromatid separation. The questions marks (?) indicate the roles of indicated proteins are not firmly established. Reproduced from Peters et al., with permission from Cold Spring Harbor Laboratory Press.

Figure 4.

The condensin complex and cell cycle regulation. (a) Condensin I (i) and condensin II (ii) share the same pair of Smc2 and Smc4 core subunits. Each of the three non‐Smc subunits of condensin I has a distantly related counterpart in those of condensin II. The CAP (chromosome‐associated protein)‐D2, CAP‐G, CAP‐D3 and CAP‐G2 subunits contain HEAT repeats, whereas the CAP‐H and CAP‐H2 subunits belong to the kleisin family of proteins. (b) The ‘traditional’ classification of mitosis and subcellular distributions of condensins I and II during the cell cycle. Nuclear envelope breakdown (NEBD), one of the key events in early mitosis, occurs at the transition from prophase (pro) to prometaphase (prometa) in this classification. The distributions of condensin I and condensin II complexes are shown in blue and magenta, respectively. (c) Sequential activation of cyclin A‐Cdk1 and cyclin B‐Cdk1 during mitosis. (d) Hypothesised activities of condensins I and II during mitosis. According to this model, condensin II is responsible for prophase condensation, which may involve reversible, hierarchical folding. Upon NEBD, condensin I gains access to chromosomes and cooperates with condensin II to build fully resolved sister chromatids. This process accompanies the formation of the chromatid axis and cannot be reversed by DNA damage. (e) A classification of mitotic stages proposed by Pines and Rieder (Pines and Rieder, ), which emphasises the ‘point of no return’ that makes the final commitment to mitosis. Reproduced from Hirano , with permission from Elsevier.

Figure 5.

The centrosomes, spindle microtubules and chromosome movement during mitosis. (a) Prophase division of the centrosome and migration of the new centrosomes around the nuclear envelope to form the spindle poles. Interactions between molecular motors and the microtubules originating from the two separating centrosomes provide the force for this movement. (b) Prometaphase mitotic spindle. Note that the nuclear envelope has dissolved and the sister chromatids are attaching to the kinetochore microtubules, some of which are bi‐oriented while others are not. (c) Metaphase chromosomes are aligned at the equator but still oscillate. (d) Sister chromatids separate and move towards opposite poles in anaphase. The arrows show the direction of the force vectors generated by each of three types of microtubules. The astral microtubules connect the opposing spindle poles to their adjacent plasma membranes. The K‐fibres connect the kinetochore(s) of each chromosome to the spindle poles. The overlapping polar microtubules elongate and separate the spindle poles.



Alberts B (2009) Essential Cell Biology. New York: Garland Science.

Allison DC and Nestor AL (1999) Evidence for a relatively random array of human chromosomes on the mitotic ring. Journal of Cell Biology 145(1): 1–14.

Burton JL and Solomon MJ (2007) Mad3p, a pseudosubstrate inhibitor of APCCdc20 in the spindle assembly checkpoint. Genes & Development 21(6): 655–667.

Cheeseman IM, Chappie JS, Wilson‐Kubalek EM and Desai A (2006) The conserved KMN network constitutes the core microtubule‐binding site of the kinetochore. Cell 127(5): 983–997.

Clarke PR and Zhang C (2008) Spatial and temporal coordination of mitosis by Ran GTPase. Nature Reviews. Molecular Cell Biology 9(6): 464–477.

Croft JA, Bridger JM, Boyle S et al. (1999) Differences in the localization and morphology of chromosomes in the human nucleus. Journal of Cell Biology 145(6): 1119–1131.

Dorsett D and Krantz ID (2009) On the molecular etiology of Cornelia de Lange syndrome. Annals of the New York Academy of Sciences 1151: 22–37.

Fuller BG, Lampson MA, Foley EA et al. (2008) Midzone activation of aurora B in anaphase produces an intracellular phosphorylation gradient. Nature 453(7198): 1132–1136.

Gassmann R, Vagnarelli P, Hudson D and Earnshaw WC (2004) Mitotic chromosome formation and the condensin paradox. Experimental Cell Research 296(1): 35–42.

Haering CH, Lowe J, Hochwagen A and Nasmyth K (2002) Molecular architecture of SMC proteins and the yeast cohesin complex. Molecular Cell 9(4): 773–788.

Herzog F, Primorac I, Dube P et al. (2009) Structure of the anaphase‐promoting complex/cyclosome interacting with a mitotic checkpoint complex. Science 323(5920): 1477–1481.

Hirano T (2005) Condensins: organizing and segregating the genome. Current Biology 15(7): R265–R275.

Hirano T and Mitchison TJ (1994) A heterodimeric coiled‐coil protein required for mitotic chromosome condensation in vitro. Cell 79(3): 449–458.

Jansen LE, Black BE, Foltz DR and Cleveland DW (2007) Propagation of centromeric chromatin requires exit from mitosis. Journal of Cell Biology 176(6): 795–805.

Kalab P, Weis K and Heald R (2002) Visualization of a Ran‐GTP gradient in interphase and mitotic Xenopus egg extracts. Science 295(5564): 2452–2456.

Kapoor TM and Compton DA (2002) Searching for the middle ground: mechanisms of chromosome alignment during mitosis. Journal of Cell Biology 157(4): 551–556.

Kapoor TM, Lampson MA, Hergert P et al. (2006) Chromosomes can congress to the metaphase plate before biorientation. Science 311(5759): 388–391.

Kozlowski C, Srayko M and Nedelec F (2007) Cortical microtubule contacts position the spindle in C. elegans embryos. Cell 129(3): 499–510.

Kueng S, Hegemann B, Peters BH et al. (2006) Wapl controls the dynamic association of cohesin with chromatin. Cell 127(5): 955–967.

Levesque AA and Compton DA (2001) The chromokinesin kid is necessary for chromosome arm orientation and oscillation, but not congression, on mitotic spindles. Journal of Cell Biology 154(6): 1135–1146.

Liu S‐T and Yen TJ (2008) The kinetochore as target for cancer drug development. In: DeWulf PWCE (eds) The Kinetochore. New York: Springer.

Luo X and Yu H (2008) Protein metamorphosis: the two‐state behavior of Mad2. Structure 16(11): 1616–1625.

Mao Y, Abrieu A and Cleveland DW (2003) Activating and silencing the mitotic checkpoint through CENP‐E‐dependent activation/inactivation of BubR1. Cell 114(1): 87–98.

Mao Y, Desai A and Cleveland DW (2005) Microtubule capture by CENP‐E silences BubR1‐dependent mitotic checkpoint signaling. Journal of Cell Biology 170(6): 873–880.

Mapelli M and Musacchio A (2007) Mad contortions: conformational dimerization boosts spindle checkpoint signaling. Current Opinion in Structural Biology 17(6): 716–725.

McIntosh JR, Grishchuk EL and West RR (2002) Chromosome‐microtubule interactions during mitosis. Annual Review of Cell and Developmental Biology 18: 193–219.

Mikhailov A, Shinohara M and Rieder CL (2005) The p38‐mediated stress‐activated checkpoint. A rapid response system for delaying progression through antephase and entry into mitosis. Cell Cycle 4(1): 57–62.

Musacchio A and Salmon ED (2007) The spindle‐assembly checkpoint in space and time. Nature Reviews. Molecular Cell Biology 8(5): 379–393.

Nestor AL, Hollopeter SL, Matsui SI and Allison D (2007) A model for genetic complementation controlling the chromosomal abnormalities and loss of heterozygosity formation in cancer. Cytogenetic Genome Research 116(4): 235–247.

Peters JM, Tedeschi A and Schmitz J (2008) The cohesin complex and its roles in chromosome biology. Genes & Development 22(22): 3089–3114.

Pines J and Rieder CL (2001) Re‐staging mitosis: a contemporary view of mitotic progression. Nature Cell Biology 3(1): E3–E6.

Powers AF, Franck AD and Gestaut DR (2009) The ndc80 kinetochore complex forms load‐bearing attachments to dynamic microtubule tips via biased diffusion. Cell 136(5): 865–875.

Siller KH and Doe CQ (2009) Spindle orientation during asymmetric cell division. Nature Cell Biology 11(4): 365–374.

Stumpff J, von Dassow G, Wagenbach M, Asbury C and Wordeman L (2008) The kinesin‐8 motor Kif18A suppresses kinetochore movements to control mitotic chromosome alignment. Developmental Cell 14(2): 252–262.

Sudakin V, Chan GK and Yen TJ (2001) Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2. Journal of Cell Biology 154(5): 925–936.

Uhlmann F (2009) A matter of choice: the establishment of sister chromatid cohesion. EMBO Reports 10(10): 1095–1102.

Walczak CE and Heald R (2008) Mechanisms of mitotic spindle assembly and function. International Review of Cytology 265: 111–158.

Zhang N, Kuznetsov SG, Sharan SK et al. (2008) A handcuff model for the cohesin complex. Journal of Cell Biology 183(6): 1019–1031.

Further Reading

De Wulf P and Earnshaw WC (2009) The Kinetochore: From Molecular Discoveries to Cancer Therapy. New York: London, Springer.

Lodish HF (2008) Molecular Cell Biology. New York: W.H. Freeman.

Pollard TD, Earnshaw WC and Lippincott‐Schwartz J (2009) Cell Biology, 2nd edn. Saunders: Philadelphia.

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Liu, Song‐Tao, Allison, David C, and Nestor‐Kalinoski, Andrea L(Nov 2010) Chromosomes during Cell Division. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005770.pub2]