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Nat Struct Mol Biol. 2019 Apr;26(4):267-274. doi: 10.1038/s41594-019-0201-6. Epub 2019 Apr 1.

PICH and TOP3A cooperate to induce positive DNA supercoiling.

Author information

1
Center for Chromosome Stability & Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark. ahb@sund.ku.dk.
2
Laboratoire de Physique de l'Ecole Normale Supérieure, Université PSL, CNRS, Sorbonne Université, Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
3
Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Département de Biologie, École Normale Supérieure, CNRS, INSERM, Paris, France.
4
Nano-Science Center, Department of Chemistry, University of Copenhagen, Copenhagen, Denmark.
5
Center for Chromosome Stability & Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
6
Center for Chromosome Stability & Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark. iandh@sund.ku.dk.

Abstract

All known eukaryotic topoisomerases are only able to relieve torsional stress in DNA. Nevertheless, it has been proposed that the introduction of positive DNA supercoiling is required for efficient sister-chromatid disjunction by Topoisomerase 2a during mitosis. Here we identify a eukaryotic enzymatic activity that introduces torsional stress into DNA. We show that the human Plk1-interacting checkpoint helicase (PICH) and Topoisomerase 3a proteins combine to create an extraordinarily high density of positive DNA supercoiling. This activity, which is analogous to that of a reverse-gyrase, is apparently driven by the ability of PICH to progressively extrude hypernegatively supercoiled DNA loops that are relaxed by Topoisomerase 3a. We propose that this positive supercoiling provides an optimal substrate for the rapid disjunction of sister centromeres by Topoisomerase 2a at the onset of anaphase in eukaryotic cells.

PMID:
30936532
DOI:
10.1038/s41594-019-0201-6

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