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Self-organization of domain structures by DNA-loop-extruding enzymes.

Alipour E, Marko JF - Nucleic Acids Res. (2012)

Bottom Line: If these machines do not dissociate from DNA (infinite processivity), a disordered, exponential steady-state distribution of small loops is obtained.The size of the resulting domain can be simply regulated by boundary elements, which halt the progress of the extrusion machines.This mechanism could explain the geometrically uniform folding of eukaryote mitotic chromosomes, through extrusion of pre-programmed loops and concomitant chromosome compaction.

View Article: PubMed Central - PubMed

Affiliation: Center for Cell Analysis and Modeling, University of Connecticut Health Sciences Center, Farmington, CT 06030, USA. elnaz.alipour@gmail.com

ABSTRACT
The long chromosomal DNAs of cells are organized into loop domains much larger in size than individual DNA-binding enzymes, presenting the question of how formation of such structures is controlled. We present a model for generation of defined chromosomal loops, based on molecular machines consisting of two coupled and oppositely directed motile elements which extrude loops from the double helix along which they translocate, while excluding one another sterically. If these machines do not dissociate from DNA (infinite processivity), a disordered, exponential steady-state distribution of small loops is obtained. However, if dissociation and rebinding of the machines occurs at a finite rate (finite processivity), the steady state qualitatively changes to a highly ordered 'stacked' configuration with suppressed fluctuations, organizing a single large, stable loop domain anchored by several machines. The size of the resulting domain can be simply regulated by boundary elements, which halt the progress of the extrusion machines. Possible realizations of these types of molecular machines are discussed, with a major focus on structural maintenance of chromosome complexes and also with discussion of type I restriction enzymes. This mechanism could explain the geometrically uniform folding of eukaryote mitotic chromosomes, through extrusion of pre-programmed loops and concomitant chromosome compaction.

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Treadmilling as an alternative to individual machine translocation. Binding of machines with ATP bound (black machines) leads to multiple-machine cluster [(a–d)]; ATP hydrolysis [gray machine in (d)] followed by machine release (e) leads to effective translocation of a machine cluster and formation of a loop domain, following a mechanism similar to treadmilling of monomers of cytoskeletal filaments. Numbers indicate binding order of machines in a cluster.
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gks925-F7: Treadmilling as an alternative to individual machine translocation. Binding of machines with ATP bound (black machines) leads to multiple-machine cluster [(a–d)]; ATP hydrolysis [gray machine in (d)] followed by machine release (e) leads to effective translocation of a machine cluster and formation of a loop domain, following a mechanism similar to treadmilling of monomers of cytoskeletal filaments. Numbers indicate binding order of machines in a cluster.

Mentions: Figure 7 sketches this process, where the triangular binding sites indicate the role of the asymmetric shape of condensins in regulating an asymmetric ‘elongation’ process (this asymmetry was present for the translocating machines discussed above in the directed motion of the motor elements). The combination of structural asymmetry and ATP hydrolysis could drive ‘directional polymerization’ of condensins on chromatin so as to move condensin clusters along DNA by a treadmilling process reminiscent of cytoskeletal filament polymerization (44).Figure 7.


Self-organization of domain structures by DNA-loop-extruding enzymes.

Alipour E, Marko JF - Nucleic Acids Res. (2012)

Treadmilling as an alternative to individual machine translocation. Binding of machines with ATP bound (black machines) leads to multiple-machine cluster [(a–d)]; ATP hydrolysis [gray machine in (d)] followed by machine release (e) leads to effective translocation of a machine cluster and formation of a loop domain, following a mechanism similar to treadmilling of monomers of cytoskeletal filaments. Numbers indicate binding order of machines in a cluster.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3526278&req=5

gks925-F7: Treadmilling as an alternative to individual machine translocation. Binding of machines with ATP bound (black machines) leads to multiple-machine cluster [(a–d)]; ATP hydrolysis [gray machine in (d)] followed by machine release (e) leads to effective translocation of a machine cluster and formation of a loop domain, following a mechanism similar to treadmilling of monomers of cytoskeletal filaments. Numbers indicate binding order of machines in a cluster.
Mentions: Figure 7 sketches this process, where the triangular binding sites indicate the role of the asymmetric shape of condensins in regulating an asymmetric ‘elongation’ process (this asymmetry was present for the translocating machines discussed above in the directed motion of the motor elements). The combination of structural asymmetry and ATP hydrolysis could drive ‘directional polymerization’ of condensins on chromatin so as to move condensin clusters along DNA by a treadmilling process reminiscent of cytoskeletal filament polymerization (44).Figure 7.

Bottom Line: If these machines do not dissociate from DNA (infinite processivity), a disordered, exponential steady-state distribution of small loops is obtained.The size of the resulting domain can be simply regulated by boundary elements, which halt the progress of the extrusion machines.This mechanism could explain the geometrically uniform folding of eukaryote mitotic chromosomes, through extrusion of pre-programmed loops and concomitant chromosome compaction.

View Article: PubMed Central - PubMed

Affiliation: Center for Cell Analysis and Modeling, University of Connecticut Health Sciences Center, Farmington, CT 06030, USA. elnaz.alipour@gmail.com

ABSTRACT
The long chromosomal DNAs of cells are organized into loop domains much larger in size than individual DNA-binding enzymes, presenting the question of how formation of such structures is controlled. We present a model for generation of defined chromosomal loops, based on molecular machines consisting of two coupled and oppositely directed motile elements which extrude loops from the double helix along which they translocate, while excluding one another sterically. If these machines do not dissociate from DNA (infinite processivity), a disordered, exponential steady-state distribution of small loops is obtained. However, if dissociation and rebinding of the machines occurs at a finite rate (finite processivity), the steady state qualitatively changes to a highly ordered 'stacked' configuration with suppressed fluctuations, organizing a single large, stable loop domain anchored by several machines. The size of the resulting domain can be simply regulated by boundary elements, which halt the progress of the extrusion machines. Possible realizations of these types of molecular machines are discussed, with a major focus on structural maintenance of chromosome complexes and also with discussion of type I restriction enzymes. This mechanism could explain the geometrically uniform folding of eukaryote mitotic chromosomes, through extrusion of pre-programmed loops and concomitant chromosome compaction.

Show MeSH
Related in: MedlinePlus