Chromosome Mechanics

Abstract

Chromosome mechanics describes the processes of chromosome replication and interactions during somatic cell division and gametogenesis. Mitosis can be divided into two phases consisting of nuclear and cytoplasmic division ultimately producing identical diploid somatic cells. Segregation during mitosis is largely dependent on chromosomal attachment to the mitotic spindle with a fully developed kinetochore structure. This is in contrast to meiosis where cells undergo two rounds of nuclear division to produce haploid germ cells. During this process, homologous chromosomes pair at the cellular midline allowing for exchange of deoxyribonucleic acid (DNA) between parental alleles and stabilisation of the chromosome structures during separation. Aberrations occurring in either mitosis or meiosis can result in numerical abnormalities (from nondisjunction events) which often result in nonviable offspring. However, there are some aneuploidies that are viable with trisomy 21 being the most common example of this. Similarly, unrepaired DNA damage resulting in chromosomal breakage and structural rearrangements. These large‐scale genetic changes reduce the genetic efficacy of a cell ultimately leading to cancer or cell death. In summary, mitosis and meiosis are integral parts of the cellular life cycle and both processes are essential at maintaining genomic stability within an organism.

Key Concepts

  • The cell cycle comprises two main phases: mitosis, where cell division occurs, and interphase, which includes DNA replication and the expression of many essential proteins. Interphase can be further divided into G1, S and G2.
  • Cyclin‐dependent kinases regulate progression through the cell cycle at three major checkpoints: G1, G2 and a spindle checkpoint during mitosis.
  • Mitosis is the process of cell division resulting in two identical diploid cells and can be divided into prophase, metaphase, anaphase and telophase.
  • Meiosis is the process of cell division that results in germline cells where following one round to DNA replication, the cell undergoes two cell divisions.
  • Meiosis in males results in four identical haploid cells, while meiosis in females produces a single mature ovum and three polar bodies.
  • Aberrations in either mitosis or meiosis can result in nondisjunction resulting in aneuploidy.
  • Defects in DNA repair mechanisms can also result in chromosome damage or breaking which will negatively impact the process of cell division.

Keywords: mitosis; meiosis; recombination; nondisjunction; spermatogenesis; oogenesis; homologous recombination; DNA damage

Figure 1. The stages of mitosis during the normal cell cycle. Cells enter mitosis from a resting state into interphase, the stage in which DNA (deoxyribonucleic acid) is replicated. Chromosomes (shown in green) become visible in early prophase and continue to condense through late prophase. During prophase, the spindle is formed by the two centrioles, and in late prophase, the nuclear membrane breaks down. Replicated chromosomes align on the equatorial plane during metaphase, sister chromatids disjoin during anaphase and cell division is completed in telophase, leaving two identical daughter cells that return to interphase.
Figure 2. The regulation of mitosis (M) and the interphase phases of Gap 1 (G1), Synthesis (S) and Gap 2 (G2) depends on numerous checkpoints. Mitotic cyclin‐dependent kinases (Cdks) and their associated cyclins (Cyc) regulate progression from one phase of mitosis to another. Cdk2/CycE control progression from G1 to S; CycA,B/Cdk1 from S to G2. APC/C regulates chromosome segregation through degradation of proteins such as CycB that permits cytokinesis to progress. Mitotic checkpoint genes such as BUB and MAD produce proteins that inhibit the activity of APC/C.
Figure 3. Sister chromatids are held together by cohesins to ensure the proper orientation of the chromosomes on the spindle and their separation at anaphase. Release of the cohesin complexes in the arms is accomplished by phosphorylation, while those at the centromeres require the action of separase, which is activated after its inhibitor, securin, is degraded.
Figure 4. The stages of meiosis during gametogenesis. Cells enter prophase I after DNA replication, although the chromosomes appear as single strands. Homologues begin to pair in zygotene, with chiasmata (points of recombination or crossing over) becoming evident as chromosomes continue to condense during pachytene. Further condensation and separation cause individual chromatids to become distinct during diplotene. A second decondensation occurs in the female during dictyotene that lasts for decades. Recondensation and movement of the chiasmata towards the chromosome ends take place during diakinesis. Paired homologues, each with two chromatids, line up on the equatorial plate during metaphase, and homologues disjoin towards the two poles during anaphase I. Telophase I (not shown) is generally very short and is punctuated by completion of cell division. Chromosome behaviour during the second phase of meiosis is strikingly similar to that in mitosis except that there are only 23 chromosomes present, each composed of two chromatids that disjoin at anaphase II to form haploid gametes.
Figure 5. Meiotic nondisjunction results in trisomy (47 chromosomes) or monosomy (45 chromosomes) after fertilisation of the aneuploid gamete with a normal gamete. (a) Normal segregation (disjunction) of one pair of acrocentric chromosomes. One chromosome has satellites on the short arm to distinguish the two members of the pair. These represent a heterozygous marker near the centromeres. (b) Nondisjunction at meiosis I (MI). Note that the marker satellites are heterozygous in the gametes. (c) Nondisjunction at meiosis II (MII). Note that the marker satellites are homozygous in the gametes.
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References

Afonso O, Figueiredo AC and Maiato H (2016) Late mitotic functions of Aurora kinases. Chromosoma Apr22: 1–11. http://doi.org/10.1007/s00412‐016‐0594‐5.

Baker DJ, Dawlaty MM, Galardy P and Van Deursen JM (2007) Mitotic regulation of the anaphase‐promoting complex. Cellular and Molecular Life Sciences 64 (5): 589–600. http://doi.org/10.1007/s00018‐007‐6443‐1.

Bartek J, Lukas C and Lukas J (2004) Checking on DNA damage in S phase. Nature Reviews. Molecular Cell Biology 5 (10): 792–804. http://doi.org/10.1038/nrm1493.

Bartek J and Lukas J (2007) DNA damage checkpoints: from initiation to recovery or adaptation. Current Opinion in Cell Biology 19 (2): 238–245. http://doi.org/10.1016/j.ceb.2007.02.009.

Chan GK and Yen TJ (2003) The mitotic checkpoint: a signaling pathway that allows a single unattached kinetochore to inhibit mitotic exit. Progress in Cell Cycle Research 5: 431–439. http://www.ncbi.nlm.nih.gov/pubmed/14593737.

Ciccia A and Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Molecular Cell 40 (2): 179–204. http://doi.org/10.1016/j.molcel.2010.09.019.

Feichtinger M, Stopp T, Göbl C, et al. (2015) Increasing live birth rate by preimplantation genetic screening of pooled polar bodies using array comparative genomic hybridization. PLoS One 10 (5): e0128317. http://doi.org/10.1371/journal.pone.0128317.

Gardner RJM and Sutherland GR (2004) Chromosome Abnormalities and Genetic Counseling, 3rd edn, pp. 366–368. New York: Oxford University Press. ISBN‐13: 978-0195149609.

Gruhn JR, Al‐Asmar N, Fasnacht R, et al. (2016) Correlations between synaptic initiation and meiotic recombination: a study of humans and mice. American Journal of Human Genetics 98 (1): 102–115. http://doi.org/10.1016/j.ajhg.2015.11.019.

Hook EB and Hamerton JL (1977) The frequency of chromosome abnormalities detected in consecutive newborn studies – differences between studies – results by sex and severity of phenotypic involvement. In: Hook EB and Porter IH (eds) Population Cytogenetics: Studies in Humans, pp. 63–79. New York: Academic Press.

Jacobs PA and Hassold TJ (1995) The origin of numerical chromosome abnormalities. Advances in Genetics 33: 101–133.

Karampetsou E, Morrogh D, Ballard T, et al. (2014) Confined placental mosaicism: implications for fetal chromosomal analysis using microarray comparative genomic hybridization. Prenatal Diagnosis 31: 98–101. http://doi.org/10.1002/pd.4255.

Lapunzina P and Monk D (2011) The consequences of uniparental disomy and copy number neutral loss‐of‐heterozygosity during human development and cancer. Biology of the Cell 103: 303–317. http://doi.org/10.1042/BC20110013.

Maiburg M, Repping S and Giltay J (2012) The genetic origin of Klinefelter syndrome and its effect on spermatogenesis. Fertility and Sterility 98 (2): 253–260. http://doi.org/10.1016/j.fertnstert.2012.06.019.

Metzler‐Guillemain C, Usson Y, Mignon C, et al. (2000) Organization of the X and Y chromosomes in human, chimpanzee and mouse pachytene nuclei using molecular cytogenetics and three‐dimensional confocal analyses. Chromosome Research: An International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology 8 (7): 571–584.

Musacchio A and Salmon ED (2007) The spindle‐assembly checkpoint in space and time. Nature Reviews. Molecular Cell. Biology 8 (5): 379–393. http://doi.org/10.1038/nrm2163.

Nagaoka T, Hassold P and Hunt P (2012) Human aneuploidy: mechanism and new insights into an age old problem. Nature reviews Genetics 13 (7): 493–504.

Nezi L and Musacchio A (2009) Sister chromatid tension and the spindle assembly checkpoint. Current Opinion in Cell Biology 21 (6): 785–795. http://doi.org/10.1016/j.ceb.2009.09.007.

Orlando DA, Lin CY, Bernard A, et al. (2008) Global control of cell‐cycle transcription by coupled CDK and network oscillators. Nature 453 (7197): 944–947. 10.1038/nature06955.

Pines J (2006) Mitosis: a matter of getting rid of the right protein at the right time. Trends in Cell Biology 16 (1): 55–63. http://doi.org/10.1016/j.tcb.2005.11.006.

Vallente RU, Cheng EY and Hassold TJ (2006) The synaptonemal complex and meiotic recombination in humans: new approaches to old questions. Chromosoma 115 (3): 241–249. http://doi.org/10.1007/s00412‐006‐0058‐4.

Warmerdam DO and Kanaar R (2010) Dealing with DNA damage: relationships between checkpoint and repair pathways. Mutation Research 704 (1‐3): 2–11. http://doi.org/10.1016/j.mrrev.2009.12.001.

Wei H and Yu X (2016) Functions of PARylation in DNA damage repair pathways. Genomics, Proteomics & Bioinformatics 14 (3): 131–139. http://doi.org/10.1016/j.gpb.2016.05.001.

Zanders SE and Malik HS (2015) Chromosome segregation: human female meiosis breaks all the rules. Current Biology 25 (15): R654–R656. http://doi.org/10.1016/j.cub.2015.06.054.

Further Reading

Campbell NA and Reece JB (2010) Biology, 9th edn. Menlo Park, CA: Benjamin Cummings. ISBN‐13: 978-0321558237.

Lodish H, Scott MP, Matsudaira P, et al. (2013) Molecular Cell Biology, 7th edn. New York: WH Freeman & Co. ISBN 9781464102288.

Moore KL and Persaud TVN (2013) The Developing Human, Clinically Oriented Embryology, 9th edn. Philadelphia, PA: WB Saunders. ISBN‐13: 978-143772002.

Pines J, Hyman A and Yanagida M (2015) Mitosis, 1st edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. ISBN‐13: 978-1621820154.

Stein GS and Pardee AB (eds) (2004) Cell Cycle and Growth Control: Biomolecular Regulation and Cancer, 2nd edn. Hoboken, NJ: John Wiley‐Liss. ISBN‐13: 978-0471250715.

Vogel F and Motulsky AG (2010) Human Genetics. Problems and Approaches, 4th edn. Berlin: Springer. ISBN‐13: 978-354037653.

Zhong A, Tan FQ and Yang WX (2016) Chromokinesin: kinesin superfamily regulating cell division through chromosome and spindle. Gene 16: 30392–30394.

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LeClair, Renée J, and Best, Robert G(Nov 2016) Chromosome Mechanics. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001441.pub3]