The Mitotic Chromosome: Structure and Mechanics

Biophysics of protein–DNA interactions and chromosome organization

“…During cell division, eukaryote chromosomes become completely segregated from one another, despite the fact that following DNA replication, the chromosomes are released from being tethered to the inside of the nuclear envelope, and have an opportunity to entangle with one another [122]. Evidence for inter-chromosome entanglements have been obtained from experiments in fission yeast where the DNA-topology-changing enzyme topo II was disabled during chromosome condensation: different chromosomes were observed to be unable to segregate from one another [123].…”

“…[122]). This process of “chromosome condensation” is thought to be coupled to the process of segregation of chromosomes from one another [127, 128, 129, 122] as well as to separation of sister chromatids from one another inside each chromosome The peculiar type of “condensation” that occurs - “lengthwise compaction”, or folding of chromosomes along their length - ensures separation of different chromosomes, provided that topo II is present during the compaction process This should be contrasted with the manner of condensation discussed in polymer physics (“poor solvent” or “polymer melt” conditions) whereby all segments stick to one another; if this occurred to chromosomes they would become hopelessly entangled with one another, as occurs in a polymer melt [130]. …”

Polymer model with long-range interactions: Analysis and applications to the chromatin structure

“…Indeed, these proteins are capable of generating large hoops that tie together sites far apart along the chromosome. During mitosis, the concentration of the condensin increases, resulting in an increase young modulus of the chromosome [21]. Another application of the β-model is to re-interpret the interactions map of the human genome [22].…”

Compaction and segregation of sister chromatids via active loop extrusion

“…formation of two separate chromosomal bodies. Finally, originally intertwined sister chromatids become topologically disentangled, which is surprising, given the general tendency of polymers to become more intertwined as they are concentrated ( Marko, 2011 ).…”

“…None of these features cannot be produced by indiscriminate cross-linking of chromosomes ( Marko and Siggia, 1997 ), which suggests that a novel mechanism of polymer compaction must occur, namely 'lengthwise compaction' ( Marko, 2009 ; 2011 ; Marko and Rippe, 2011 ), which permits each chromatid to be compacted while avoiding sticking of separate chromatids together. Cell-biological studies suggest that topoisomerase II and condensin are essential for metaphase chromosome compaction ( Hirano and Mitchison, 1993 ; 1994 ; Wood and Earnshaw, 1990 ; Hirano, 1995 ), leading to the hypothesis that mitotic compaction-segregation relies on the interplay between the activities of these two protein complexes.…”