Structural Changes in Chromosomes Driven by Multiple Condensin Motors During Mitosis

Dey, Atreya; Shi, Guang; Takaki, Ryota; Thirumalai, D.

doi:10.2139/ssrn.4170191

Cited by 4 publications

(4 citation statements)

References 54 publications

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“…We anticipate that the direction changes described here are essential for proper genome organization by SMC complexes 55 . Simulations have shown that unidirectional extruders are unable to recapitulate the experimentally observed interphase chromosome organization, in particular the formation of TADs, even if the anchor site is only diffusively bound to DNA 56 , while asymmetric extrusion with Z-loop formation and direction switching could recapitulate mitotic chromosome formation 56,57 . In contrast, asymmetric extrusion with switching adequately reproduces the interphase chromosome organization.…”

Section: The Physiological Relevance Of Extrusion Direction Switchingmentioning

confidence: 98%

SMC motor proteins extrude DNA asymmetrically and contain a direction switch

Barth,

Davidson,

van der Torre

et al. 2023

Preprint

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SummaryStructural Maintenance of Chromosomes (SMC) complexes organize the genomeviaDNA loop extrusion. While some SMCs were reported to do so symmetrically, reeling DNA from both sides into the extruded DNA loop simultaneously, others perform loop extrusion asymmetrically toward one direction only. The mechanism underlying this variability remains unclear. Here, we examine the directionality of DNA loop extrusion by SMCs usingin vitrosingle-molecule experiments. We find that cohesin and SMC5/6 do not reel in DNA from both sides, as reported before, but instead extrude DNA asymmetrically, while the direction can switch over time. Asymmetric DNA loop extrusion thus is the shared mechanism across all eukaryotic SMC complexes. For cohesin, direction switches strongly correlate with the turnover of the subunit NIPBL, during which DNA strand switching may occur. STAG1 stabilizes NIPBL on cohesin, preventing NIPBL turnover and direction switches. The findings reveal that SMCs, surprisingly, contain a direction switch subunit.HighlightsAll eukaryotic SMC complexes extrude DNA asymmetrically.Apparent ‘symmetric’ loop extrusion is the result of frequent direction switches.n human cohesin, loop-extrusion direction changes require exchange of NIPBL.STAG1 stabilizes NIPBL on human cohesin.

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Section: The Physiological Relevance Of Extrusion Direction Switchingmentioning

confidence: 98%

SMC motor proteins extrude DNA asymmetrically and contain a direction switch

Barth,

Davidson,

van der Torre

et al. 2023

Preprint

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show abstract

“…SMC complexes are motor proteins that extrude loops of DNA to organize chromatin into higher-order structures [13][14][15][16][17][18][19][20] . Condensin compacts chromosomes during mitosis via DNA loop extrusion [21][22][23][24][25] and is essential to chromosome segregation 26,27 . Condensin consists of two ATPase SMC coiled-coil subunits (Smc2 and Smc4), a kleisin (Brn1 in budding yeast), and two HEAT-repeat subunits (Ycs4 and Ycg1 in budding yeast).…”

Section: Mainmentioning

confidence: 99%

Telomere protein arrays stall DNA loop extrusion by condensin

Analikwu,

Deshayes,

van der Torre

et al. 2023

Preprint

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DNA loop extrusion by SMC proteins is a key process underlying chromosomal organization. It is unknown how loop extruders interact with telomeres where chromosome ends are covered with a dense array of tens of neighboring DNA-binding proteins. Using complementaryin vivoandin vitrosingle-molecule approaches, we study the interaction between loop-extruding condensin and arrays of Rap1, the double-stranded-DNA-binding telomeric protein ofSaccharomyces cerevisiae. We show that dense linear Rap1 arrays can completely halt DNA loop extrusion, where the blocking efficiency depends on the array length and the DNA gap size between neighboring proteins. In cells, Rap1 arrays in the chromosome are found to act as contact insulators and to accumulate condensin at their borders, with direct implications for the resolution of dicentric chromosomes produced by telomere fusions. Our findings show that linear arrays of DNA-bound proteins can efficiently halt DNA loop extrusion by SMC proteins, which may impact a wide range of cellular processes from telomere functions to transcription and DNA repair.

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“…In our model, the loop topology does not change with time, unlike polymer models, which examined the consequences of dynamic extrusion of loops on interphase and mitotic structures (34)(35)(36). We simulate a given chromosome region up to ∼10 seconds (see Methods for details) that is much shorter than the lifetime of the CTCF loops (15-30 mins) (37,38).…”

Section: Modelmentioning

confidence: 99%

Transcription-induced active forces suppress chromatin motion

Shin

Cho

Shi

et al. 2022

Preprint

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Recent experiments have shown that the mobility of human interphase chromosome decreases during transcription, and increases upon inhibiting transcription, a finding that is counter-intuitive because it is thought that the active mechanical force (F) generated by RNA polymerase II (RNAPII) on chromatin would render it more open and mobile. We use a polymer model to investigate how F, derived from transcriptional activity, affects the dynamical properties of chromatin. The movements of the loci in the gene-rich region are suppressed in an intermediate range of F, and are enhanced at small and large F values. In the intermediate F, the bond length between consecutive loci increases, becoming commensurate with the location of the minimum in the attractive interaction between the active loci in the chromatin. This results in a disorder-to-order transition, leading to the decreased mobility during transcription. Our results suggest that transient ordering of the loci in the generich region might be a mechanism for nucleating a dynamic network involving transcription factors, RNAPII, and chromatin.

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Structural Changes in Chromosomes Driven by Multiple Condensin Motors During Mitosis

Cited by 4 publications

References 54 publications

SMC motor proteins extrude DNA asymmetrically and contain a direction switch

SMC motor proteins extrude DNA asymmetrically and contain a direction switch

Telomere protein arrays stall DNA loop extrusion by condensin

Transcription-induced active forces suppress chromatin motion

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