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Science. 2018 Feb 9;359(6376). pii: eaao6135. doi: 10.1126/science.aao6135. Epub 2018 Jan 18.

A pathway for mitotic chromosome formation.

Author information

1
Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
2
Wellcome Centre for Cell Biology, University of Edinburgh, King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, Scotland, UK.
3
Institute for Medical Engineering and Science and Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
4
Division of Molecular Cell Engineering, National Institute of Genetics, Research Organization of Information and Systems, and Department of Genetics, SOKENDAI, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
5
Department of Chemistry, University of Wisconsin Oshkosh, 800 Algoma Boulevard, Oshkosh, WI 54901, USA.
6
Wellcome Centre for Cell Biology, University of Edinburgh, King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, Scotland, UK. bill.earnshaw@ed.ac.uk leonid@MIT.edu job.dekker@umassmed.edu.
7
Institute for Medical Engineering and Science and Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. bill.earnshaw@ed.ac.uk leonid@MIT.edu job.dekker@umassmed.edu.
8
Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. bill.earnshaw@ed.ac.uk leonid@MIT.edu job.dekker@umassmed.edu.
9
Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.

Abstract

Mitotic chromosomes fold as compact arrays of chromatin loops. To identify the pathway of mitotic chromosome formation, we combined imaging and Hi-C analysis of synchronous DT40 cell cultures with polymer simulations. Here we show that in prophase, the interphase organization is rapidly lost in a condensin-dependent manner, and arrays of consecutive 60-kilobase (kb) loops are formed. During prometaphase, ~80-kb inner loops are nested within ~400-kb outer loops. The loop array acquires a helical arrangement with consecutive loops emanating from a central "spiral staircase" condensin scaffold. The size of helical turns progressively increases to ~12 megabases during prometaphase. Acute depletion of condensin I or II shows that nested loops form by differential action of the two condensins, whereas condensin II is required for helical winding.

PMID:
29348367
PMCID:
PMC5924687
DOI:
10.1126/science.aao6135
[Indexed for MEDLINE]
Free PMC Article

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