Self-organization of domain structures by DNA-loop-extruding enzymes
Open accessAbstract
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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The convergent rule and cohesin sliding favor a linear tracking mechanism known as the loop extrusion model.
“this favors a linear tracking mechanism,47 known as the “loop extrusion model”.8,9,48”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [48]
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- Authors
- Alipour, E., & Marko, J. F.
- Affiliations
- UConn Health (US)
- Northwestern University (US)
- Corresponding author
- Alipour, E.
- Marko, J. F.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-10-15
- Volume
- 40
- Issue
- 22
- Pages
- 11202-11212
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC3526278
- OpenAlex
- W2100148696
- Cited by
- 540
- References
- 48
- Citations by year
- 2026: 26 · 2025: 45 · 2024: 44 · 2023: 46 · 2022: 38 · 2021: 55 · 2020: 71 · 2019: 61 · 2018: 54 · 2017: 52 · 2016: 27 · 2015: 10 · 2014: 7 · 2013: 3
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Science Foundation (1206868, 1022117, 0715099)
- National Institutes of Health (MCB-1022117, DMR-1206868)
- National Cancer Institute (U54CA143869)
- Division of Materials Research (DMR-1206868)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- DNA loop extrusion, self-organization, molecular machines, DNA translocation, processivity, loop size distribution, chromosome compaction, type I restriction enzymes, boundary elements
- MeSH terms
- Chromosomes, Computer Simulation, DNA, Enzymes, Models, Genetic, Nucleic Acid Conformation
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