PICH and TOP3A cooperate to induce positive DNA supercoiling

Anna H. Bizard; Jean Francois Allemand; Tue Hassenkam; Manikandan Paramasivam; Kata Sarlós; Manika Indrajit Singh; Ian D. Hickson

doi:10.1038/s41594-019-0201-6

PICH and TOP3A cooperate to induce positive DNA supercoiling

Anna H. Bizard^*, Jean Francois Allemand, Tue Hassenkam, Manikandan Paramasivam, Kata Sarlós, Manika Indrajit Singh, Ian D. Hickson

^*Corresponding author for this work

10 Citations (Scopus)

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.

Original language	English
Journal	Nature Structural and Molecular Biology
Volume	26
Issue number	4
Pages (from-to)	267-274
Number of pages	8
ISSN	1545-9993
DOIs	https://doi.org/10.1038/s41594-019-0201-6
Publication status	Published - 2019

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title = "PICH and TOP3A cooperate to induce positive DNA supercoiling",

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.",

author = "Bizard, {Anna H.} and Allemand, {Jean Francois} and Tue Hassenkam and Manikandan Paramasivam and Kata Sarl{\'o}s and Singh, {Manika Indrajit} and Hickson, {Ian D.}",

year = "2019",

doi = "10.1038/s41594-019-0201-6",

language = "English",

volume = "26",

pages = "267--274",

journal = "Nature Structural and Molecular Biology",

issn = "1545-9993",

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TY - JOUR

T1 - PICH and TOP3A cooperate to induce positive DNA supercoiling

AU - Bizard, Anna H.

AU - Allemand, Jean Francois

AU - Hassenkam, Tue

AU - Paramasivam, Manikandan

AU - Sarlós, Kata

AU - Singh, Manika Indrajit

AU - Hickson, Ian D.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1038/s41594-019-0201-6

DO - 10.1038/s41594-019-0201-6

M3 - Journal article

C2 - 30936532

AN - SCOPUS:85063740249

SN - 1545-9993

VL - 26

SP - 267

EP - 274

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 4

ER -

PICH and TOP3A cooperate to induce positive DNA supercoiling

Abstract

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