Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases

Type II topoisomerases are essential enzymes that modulate the topological state of DNA supercoiling in all living organisms. These enzymes alter DNA topology by performing double-stranded passage reactions on over- or underwound DNA substrates. This strand passage reaction generates a transient cov...

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Main Authors: Jeffrey Y. Jian, Neil Osheroff
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/13/11199
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author Jeffrey Y. Jian
Neil Osheroff
author_facet Jeffrey Y. Jian
Neil Osheroff
author_sort Jeffrey Y. Jian
collection DOAJ
description Type II topoisomerases are essential enzymes that modulate the topological state of DNA supercoiling in all living organisms. These enzymes alter DNA topology by performing double-stranded passage reactions on over- or underwound DNA substrates. This strand passage reaction generates a transient covalent enzyme–cleaved DNA structure known as the cleavage complex. Al-though the cleavage complex is a requisite catalytic intermediate, it is also intrinsically dangerous to genomic stability in biological systems. The potential threat of type II topoisomerase function can also vary based on the nature of the supercoiled DNA substrate. During essential processes such as DNA replication and transcription, cleavage complex formation can be inherently more dangerous on overwound versus underwound DNA substrates. As such, it is important to understand the profound effects that DNA topology can have on the cellular functions of type II topoisomerases. This review will provide a broad assessment of how human and bacterial type II topoisomerases recognize and act on their substrates of various topological states.
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spelling doaj.art-4e324df2e8a248a389155c613a1193462023-11-18T16:49:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124131119910.3390/ijms241311199Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II TopoisomerasesJeffrey Y. Jian0Neil Osheroff1Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USADepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USAType II topoisomerases are essential enzymes that modulate the topological state of DNA supercoiling in all living organisms. These enzymes alter DNA topology by performing double-stranded passage reactions on over- or underwound DNA substrates. This strand passage reaction generates a transient covalent enzyme–cleaved DNA structure known as the cleavage complex. Al-though the cleavage complex is a requisite catalytic intermediate, it is also intrinsically dangerous to genomic stability in biological systems. The potential threat of type II topoisomerase function can also vary based on the nature of the supercoiled DNA substrate. During essential processes such as DNA replication and transcription, cleavage complex formation can be inherently more dangerous on overwound versus underwound DNA substrates. As such, it is important to understand the profound effects that DNA topology can have on the cellular functions of type II topoisomerases. This review will provide a broad assessment of how human and bacterial type II topoisomerases recognize and act on their substrates of various topological states.https://www.mdpi.com/1422-0067/24/13/11199DNA topoisomeraseDNA topologysupercoil handednesstype II topoisomeraseDNA relaxationDNA cleavage
spellingShingle Jeffrey Y. Jian
Neil Osheroff
Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases
International Journal of Molecular Sciences
DNA topoisomerase
DNA topology
supercoil handedness
type II topoisomerase
DNA relaxation
DNA cleavage
title Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases
title_full Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases
title_fullStr Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases
title_full_unstemmed Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases
title_short Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases
title_sort telling your right hand from your left the effects of dna supercoil handedness on the actions of type ii topoisomerases
topic DNA topoisomerase
DNA topology
supercoil handedness
type II topoisomerase
DNA relaxation
DNA cleavage
url https://www.mdpi.com/1422-0067/24/13/11199
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