Rules of engagement for condensins and cohesins guide mitotic chromosome formation

Kumiko Samejima; Johan H. Gibcus; Sameer  Abraham; Fernanda Cisneros-Soberanis; Itaru Samejima; Alison J. Beckett; Nina Pucekova; Maria Alba Abad; Maria Alba Abad; Christos Spanos; Bethan Medina-Pritchard; James R. Paulson; Linfeng Xie; Arockia A. Jeyaprakash; Ian A. Prior; Leonid A. Mirny; Job Dekker; Anton Goloborodko; William C. Earnshaw

doi:10.1126/science.adq1709

Rules of engagement for condensins and cohesins guide mitotic chromosome formation

Kumiko Samejima, Johan H. Gibcus, Sameer Abraham, Fernanda Cisneros-Soberanis, Itaru Samejima, Alison J. Beckett, Nina Pucekova, Maria Alba Abad, Maria Alba Abad, Christos Spanos, Bethan Medina-Pritchard, James R. Paulson, Linfeng Xie, Arockia A. Jeyaprakash, Ian A. Prior, Leonid A. Mirny^*, Job Dekker^*, Anton Goloborodko^*, William C. Earnshaw^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

We used Hi-C, imaging, proteomics and polymer modeling to define rules of engagement for SMC complexes as cells refold interphase chromatin into rod-shaped mitotic chromosomes. Firstly, condensin disassembles interphase chromatin loop organization by evicting or displacing extrusive cohesin. Secondly, condensin bypasses cohesive cohesins, thereby maintaining sister chromatid cohesion as sisters separate. Studies of mitotic chromosomes formed by cohesin, condensin II and condensin I alone or in combination reveal new models of mitotic chromosome conformation. In these models, loops are consecutive and not overlapping, implying that condensins stall upon encountering each other. The dynamics of Hi-C interactions and chromosome morphology reveal that during prophase loops are extruded in vivo at ~1-3 kb/sec by condensins as they form a disordered discontinuous helical scaffold within individual chromatids.

Original language	English
Article number	eadq1709
Number of pages	23
Journal	Science
Volume	388
Issue number	6743
DOIs	https://doi.org/10.1126/science.adq1709
Publication status	Published - 11 Apr 2025

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10.1126/science.adq1709

20250108_MS-FINAL-acceptedAccepted author manuscript, 1.68 MBLicence: Creative Commons: Attribution (CC-BY)

1 Active
2 Finished

Mechanistic Basis for CENP-32 Mediated Regulation of Cell Division
Arulanandam, J. (Principal Investigator), Earnshaw, B. (Co-investigator) & Tollervey, D. (Co-investigator)
Medical Research Council
1/01/23 → 31/12/25
Project: Research
Core funding for the Wellcome Centre for Cell Biology
Marston, A. (Principal Investigator)
Wellcome Trust (Rcl)
1/12/21 → 30/11/24
Project: Research
The role of non-histone proteins in chromosome structure and function during mitosis
Earnshaw, B. (Principal Investigator)
Wellcome Trust (Rcl)
1/10/15 → 30/09/21
Project: Research

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Samejima, K., Gibcus, J. H., Abraham, S., Cisneros-Soberanis, F., Samejima, I., Beckett, A. J., Pucekova, N., Abad, M. A., Abad, M. A., Spanos, C., Medina-Pritchard, B., Paulson, J. R., Xie, L., Jeyaprakash, A. A., Prior, I. A., Mirny, L. A., Dekker, J., Goloborodko, A., & Earnshaw, W. C. (2025). Rules of engagement for condensins and cohesins guide mitotic chromosome formation. Science, 388(6743), Article eadq1709 . https://doi.org/10.1126/science.adq1709

@article{ddca38a2577d4e2ea4c8fcf48a62e8aa,

title = "Rules of engagement for condensins and cohesins guide mitotic chromosome formation",

abstract = "We used Hi-C, imaging, proteomics and polymer modeling to define rules of engagement for SMC complexes as cells refold interphase chromatin into rod-shaped mitotic chromosomes. Firstly, condensin disassembles interphase chromatin loop organization by evicting or displacing extrusive cohesin. Secondly, condensin bypasses cohesive cohesins, thereby maintaining sister chromatid cohesion as sisters separate. Studies of mitotic chromosomes formed by cohesin, condensin II and condensin I alone or in combination reveal new models of mitotic chromosome conformation. In these models, loops are consecutive and not overlapping, implying that condensins stall upon encountering each other. The dynamics of Hi-C interactions and chromosome morphology reveal that during prophase loops are extruded in vivo at ~1-3 kb/sec by condensins as they form a disordered discontinuous helical scaffold within individual chromatids. ",

author = "Kumiko Samejima and Gibcus, {Johan H.} and Sameer Abraham and Fernanda Cisneros-Soberanis and Itaru Samejima and Beckett, {Alison J.} and Nina Pucekova and Abad, {Maria Alba} and Abad, {Maria Alba} and Christos Spanos and Bethan Medina-Pritchard and Paulson, {James R.} and Linfeng Xie and Jeyaprakash, {Arockia A.} and Prior, {Ian A.} and Mirny, {Leonid A.} and Job Dekker and Anton Goloborodko and Earnshaw, {William C.}",

note = "We thank David Kelly and Toni McHugh for help with light microscopy and Dr. Martin Waterfall for help with flow cytometry. Sorting of GFP positive and negative cells s ",

year = "2025",

month = apr,

day = "11",

doi = "10.1126/science.adq1709",

language = "English",

volume = "388",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

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Samejima, K, Gibcus, JH, Abraham, S, Cisneros-Soberanis, F , Samejima, I, Beckett, AJ, Pucekova, N, Abad, MA, Abad, MA , Spanos, C , Medina-Pritchard, B, Paulson, JR, Xie, L, Jeyaprakash, AA, Prior, IA, Mirny, LA, Dekker, J, Goloborodko, A & Earnshaw, WC 2025, 'Rules of engagement for condensins and cohesins guide mitotic chromosome formation', Science, vol. 388, no. 6743, eadq1709 . https://doi.org/10.1126/science.adq1709

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T1 - Rules of engagement for condensins and cohesins guide mitotic chromosome formation

AU - Samejima, Kumiko

AU - Gibcus, Johan H.

AU - Abraham, Sameer

AU - Cisneros-Soberanis, Fernanda

AU - Samejima, Itaru

AU - Beckett, Alison J.

AU - Pucekova, Nina

AU - Abad, Maria Alba

AU - Spanos, Christos

AU - Medina-Pritchard, Bethan

AU - Paulson, James R.

AU - Xie, Linfeng

AU - Jeyaprakash, Arockia A.

AU - Prior, Ian A.

AU - Mirny, Leonid A.

AU - Dekker, Job

AU - Goloborodko, Anton

AU - Earnshaw, William C.

N1 - We thank David Kelly and Toni McHugh for help with light microscopy and Dr. Martin Waterfall for help with flow cytometry. Sorting of GFP positive and negative cells s

PY - 2025/4/11

Y1 - 2025/4/11

N2 - We used Hi-C, imaging, proteomics and polymer modeling to define rules of engagement for SMC complexes as cells refold interphase chromatin into rod-shaped mitotic chromosomes. Firstly, condensin disassembles interphase chromatin loop organization by evicting or displacing extrusive cohesin. Secondly, condensin bypasses cohesive cohesins, thereby maintaining sister chromatid cohesion as sisters separate. Studies of mitotic chromosomes formed by cohesin, condensin II and condensin I alone or in combination reveal new models of mitotic chromosome conformation. In these models, loops are consecutive and not overlapping, implying that condensins stall upon encountering each other. The dynamics of Hi-C interactions and chromosome morphology reveal that during prophase loops are extruded in vivo at ~1-3 kb/sec by condensins as they form a disordered discontinuous helical scaffold within individual chromatids.

AB - We used Hi-C, imaging, proteomics and polymer modeling to define rules of engagement for SMC complexes as cells refold interphase chromatin into rod-shaped mitotic chromosomes. Firstly, condensin disassembles interphase chromatin loop organization by evicting or displacing extrusive cohesin. Secondly, condensin bypasses cohesive cohesins, thereby maintaining sister chromatid cohesion as sisters separate. Studies of mitotic chromosomes formed by cohesin, condensin II and condensin I alone or in combination reveal new models of mitotic chromosome conformation. In these models, loops are consecutive and not overlapping, implying that condensins stall upon encountering each other. The dynamics of Hi-C interactions and chromosome morphology reveal that during prophase loops are extruded in vivo at ~1-3 kb/sec by condensins as they form a disordered discontinuous helical scaffold within individual chromatids.

U2 - 10.1126/science.adq1709

DO - 10.1126/science.adq1709

M3 - Article

SN - 0036-8075

VL - 388

JO - Science

JF - Science

IS - 6743

M1 - eadq1709

ER -

Rules of engagement for condensins and cohesins guide mitotic chromosome formation

Abstract

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Projects

Mechanistic Basis for CENP-32 Mediated Regulation of Cell Division

Core funding for the Wellcome Centre for Cell Biology

The role of non-histone proteins in chromosome structure and function during mitosis

Cite this