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Nat Cell Biol. 2016 Jun;18(6):692-9. doi: 10.1038/ncb3353. Epub 2016 May 2.

Sister chromatid resolution is an intrinsic part of chromosome organization in prophase.

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Cancer Institute of the Japanese Foundation for Cancer Research, Division of Experimental Pathology, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
Tokyo Institute of Technology, Department of Biological Sciences, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan.
European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany.


The formation of mitotic chromosomes requires both compaction of chromatin and the resolution of replicated sister chromatids. Compaction occurs during mitotic prophase and prometaphase, and in prophase relies on the activity of condensin II complexes. Exactly when and how sister chromatid resolution occurs has been largely unknown, as has its molecular requirements. Here, we established a method to visualize sister resolution by sequential replication labelling with two distinct nucleotide derivatives. Quantitative three-dimensional imaging then allowed us to measure the resolution of sister chromatids throughout mitosis by calculating their non-overlapping volume within the whole chromosome. Unexpectedly, we found that sister chromatid resolution starts already at the beginning of prophase, proceeds concomitantly with chromatin compaction and is largely completed by the end of prophase. Sister chromatid resolution was abolished by inhibition of topoisomerase IIα and by depleting or preventing mitotic activation of condensin II, whereas blocking cohesin dissociation from chromosomes had little effect. Mitotic sister chromatid resolution is thus an intrinsic part of mitotic chromosome formation in prophase that relies largely on DNA decatenation and shares the molecular requirement for condensin II with prophase compaction.

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