Chromosome Condensation and Cohesion

Abstract

The diploid human genome consists of 46 chromosomes, which collectively contain about 2 m of deoxyribonucleic acid (DNA). During mitosis, the genome is packaged into 46 pairs of sister chromatids, each less than 10 μm long. Two fundamental mechanisms govern the formation and maintenance of chromosome structure during mitosis: (i) the dramatic and progressive compaction of chromosomes in the process of chromosome condensation and (ii) the establishment of the physical linkages or cohesion between the sister chromatids. Central to the processes of chromosome condensation and cohesion are the type II topoisomerases and the Structure Maintenance of Chromosomes (SMC) family of proteins, which form the condensin and cohesin complexes. These proteins cooperate to ensure chromosome condensation and cohesion, thus promoting the accurate partition of the genome during mitosis.

Key Concepts:

  • Chromosome condensation and cohesion are necessary for accurate chromosome segregation.

  • Condensin and topoisomerase IIα are the major regulators of chromosome condensation.

  • Sister‐chromatid cohesion is required for the bipolar attachment of chromosomes to the spindle microtubules and counteracts the spindle pulling forces generated at the kinetochores.

  • The cohesin complex is critical for sister‐chromatid cohesion.

  • Both DNA catenation and sister‐chromatid cohesion have to be resolved for proper sister‐chromatid separation.

  • Centromeric cohesion is regulated by the spindle checkpoint. Its removal occurs at the onset of anaphase.

Keywords: chromosome condensation; sister‐chromatid cohesion; chromosome segregation; mitosis; condensin; cohesin; topoisomerase II

Figure 1.

Chromosome dynamics during the cell cycle. Key events and their regulators are indicated. Chromosomes are decondensed in interphase. Chromosome condensation occurs at prophase and continues during mitosis, resulting in progressive compaction of the chromosomes that is rapidly reversed at telophase. Chromosome condensation is regulated by histone‐modifying enzymes, such as Aurora B and requires the cooperation of condensins I and II and Topo IIα. Sister‐chromatid cohesion is established during DNA replication and requires the cohesin complex and its regulatory proteins. DNA catenation that arises during DNA replication may contribute to sister‐chromatid cohesion. Both cohesin and DNA catenation need to be removed at the metaphase–anaphase transition to allow sister‐chromatid separation.

Figure 2.

Key regulators of chromosome condensation and cohesion. Condensin and cohesin consist of SMC proteins and mediate chromosome condensation and cohesion respectively. Condensin exists in two forms: condensins I and II. Condensins are thought to bind to DNA and introduce coils. Cohesin forms a ring. It is thought to tether the two sister chromatids by either embracing them within a single ring or by the interaction of two rings with each ring holding one sister chromatid. Topoisomerase IIα is required for both chromosome condensation and sister‐chromatid separation. It exists as a dimer and can decatenate DNA by passing a duplex DNA through another. Condensin and topoisomerase IIα were discovered as components of the axial scaffold that runs along chromosomes (right panel) and are present in alternating patches. In addition, topoisomerase IIα is highly enriched at the centromeres and this enrichment depends on its sumoylation. Cohesin is also enriched at centromeres at metaphase. Both centromeric cohesin and centromeric DNA catenation need to be resolved to allow centromere separation and anaphase onset.

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Further Reading

Georgatos SD, Markaki Y, Christogianni A et al. (2009) Chromatin remodeling during mitosis: a structure‐based code? Frontiers in Bioscience 14: 2017–2027.

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Díaz‐Martínez, Laura Angélica, and Yu, Hongtao(Dec 2010) Chromosome Condensation and Cohesion. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022534]