A pathway for mitotic chromosome formation
Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Biochemistry | Computational Biology | Molecular Biology | Structural Biology | Systems Biology
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.
DOI of Published Version
Science. 2018 Feb 9;359(6376). pii: eaao6135. doi: 10.1126/science.aao6135. Epub 2018 Jan 18. Link to article on publisher's site
Science (New York, N.Y.)
Gibcus, Johan H.; Samejima, Kumiko; Goloborodko, Anton; Samejima, Itaru; Naumova, Natalia; Nuebler, Johannes; Kanemaki, Masato T.; Xie, Linfeng; Paulson, James R.; Earnshaw, William C.; Mirny, Leonid A.; and Dekker, Job, "A pathway for mitotic chromosome formation" (2018). Program in Systems Biology Publications and Presentations. 118.