Mycobacterium tuberculosis UvrD1 and UvrD2 helicases unwind G-quadruplex DNA

Tias Saha; Kaustubh Shukla; Roshan Singh Thakur; Ambika Desingu; Ganesh Nagaraju

doi:10.1111/febs.14798

Mycobacterium tuberculosis UvrD1 and UvrD2 helicases unwind G-quadruplex DNA

Tias Saha, Kaustubh Shukla, Roshan Singh Thakur, Ambika Desingu, Ganesh Nagaraju^*

^*Corresponding author for this work

8 Citations (Scopus)

Abstract

Unresolved G-quadruplex (G4) DNA secondary structures impede DNA replication and can lead to DNA breaks and to genome instability. Helicases are known to unwind G4 structures and thereby facilitate genome duplication. Escherichia coli UvrD is a multifunctional helicase that participates in DNA repair, recombination and replication. Previously, we had demonstrated a novel role of E. coli UvrD helicase in resolving G4 structures. Mycobacterium tuberculosis genome encodes two orthologs of E. coli UvrD helicase, UvrD1 and UvrD2. It is unclear whether UvrD1 or UvrD2 or both helicases unwind G4 DNA structures. Here, we demonstrate that M. tuberculosis UvrD1 and UvrD2 unwind G4 tetraplexes. Both helicases were proficient in resolving previously characterized tetramolecular G4 structures in an ATP hydrolysis and single-stranded 3′-tail-dependent manner. Notably, M. tuberculosis UvrD1 and UvrD2 were efficient in unwinding G4 structures derived from the potential G4 forming sequences present in the M. tuberculosis genome. These data suggest an extended role for M. tuberculosis UvrD1 and UvrD2 helicases in resolving G4 DNA structures and provide insights into the maintenance of genome integrity via G4 DNA resolution.

Original language	English
Journal	FEBS Journal
ISSN	1742-464X
DOIs	https://doi.org/10.1111/febs.14798
Publication status	Published - Jun 2019
Externally published	Yes

Keywords

DNA replication and genome stability
G4 DNA
Helicases
UvrD

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/febs.14798

Cite this

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title = "Mycobacterium tuberculosis UvrD1 and UvrD2 helicases unwind G-quadruplex DNA",

abstract = "Unresolved G-quadruplex (G4) DNA secondary structures impede DNA replication and can lead to DNA breaks and to genome instability. Helicases are known to unwind G4 structures and thereby facilitate genome duplication. Escherichia coli UvrD is a multifunctional helicase that participates in DNA repair, recombination and replication. Previously, we had demonstrated a novel role of E. coli UvrD helicase in resolving G4 structures. Mycobacterium tuberculosis genome encodes two orthologs of E. coli UvrD helicase, UvrD1 and UvrD2. It is unclear whether UvrD1 or UvrD2 or both helicases unwind G4 DNA structures. Here, we demonstrate that M. tuberculosis UvrD1 and UvrD2 unwind G4 tetraplexes. Both helicases were proficient in resolving previously characterized tetramolecular G4 structures in an ATP hydrolysis and single-stranded 3′-tail-dependent manner. Notably, M. tuberculosis UvrD1 and UvrD2 were efficient in unwinding G4 structures derived from the potential G4 forming sequences present in the M. tuberculosis genome. These data suggest an extended role for M. tuberculosis UvrD1 and UvrD2 helicases in resolving G4 DNA structures and provide insights into the maintenance of genome integrity via G4 DNA resolution.",

keywords = "DNA replication and genome stability, G4 DNA, Helicases, UvrD",

author = "Tias Saha and Kaustubh Shukla and Thakur, {Roshan Singh} and Ambika Desingu and Ganesh Nagaraju",

year = "2019",

month = jun,

doi = "10.1111/febs.14798",

language = "English",

journal = "F E B S Journal",

issn = "1742-464X",

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T1 - Mycobacterium tuberculosis UvrD1 and UvrD2 helicases unwind G-quadruplex DNA

AU - Saha, Tias

AU - Shukla, Kaustubh

AU - Thakur, Roshan Singh

AU - Desingu, Ambika

AU - Nagaraju, Ganesh

PY - 2019/6

Y1 - 2019/6

N2 - Unresolved G-quadruplex (G4) DNA secondary structures impede DNA replication and can lead to DNA breaks and to genome instability. Helicases are known to unwind G4 structures and thereby facilitate genome duplication. Escherichia coli UvrD is a multifunctional helicase that participates in DNA repair, recombination and replication. Previously, we had demonstrated a novel role of E. coli UvrD helicase in resolving G4 structures. Mycobacterium tuberculosis genome encodes two orthologs of E. coli UvrD helicase, UvrD1 and UvrD2. It is unclear whether UvrD1 or UvrD2 or both helicases unwind G4 DNA structures. Here, we demonstrate that M. tuberculosis UvrD1 and UvrD2 unwind G4 tetraplexes. Both helicases were proficient in resolving previously characterized tetramolecular G4 structures in an ATP hydrolysis and single-stranded 3′-tail-dependent manner. Notably, M. tuberculosis UvrD1 and UvrD2 were efficient in unwinding G4 structures derived from the potential G4 forming sequences present in the M. tuberculosis genome. These data suggest an extended role for M. tuberculosis UvrD1 and UvrD2 helicases in resolving G4 DNA structures and provide insights into the maintenance of genome integrity via G4 DNA resolution.

AB - Unresolved G-quadruplex (G4) DNA secondary structures impede DNA replication and can lead to DNA breaks and to genome instability. Helicases are known to unwind G4 structures and thereby facilitate genome duplication. Escherichia coli UvrD is a multifunctional helicase that participates in DNA repair, recombination and replication. Previously, we had demonstrated a novel role of E. coli UvrD helicase in resolving G4 structures. Mycobacterium tuberculosis genome encodes two orthologs of E. coli UvrD helicase, UvrD1 and UvrD2. It is unclear whether UvrD1 or UvrD2 or both helicases unwind G4 DNA structures. Here, we demonstrate that M. tuberculosis UvrD1 and UvrD2 unwind G4 tetraplexes. Both helicases were proficient in resolving previously characterized tetramolecular G4 structures in an ATP hydrolysis and single-stranded 3′-tail-dependent manner. Notably, M. tuberculosis UvrD1 and UvrD2 were efficient in unwinding G4 structures derived from the potential G4 forming sequences present in the M. tuberculosis genome. These data suggest an extended role for M. tuberculosis UvrD1 and UvrD2 helicases in resolving G4 DNA structures and provide insights into the maintenance of genome integrity via G4 DNA resolution.

KW - DNA replication and genome stability

KW - G4 DNA

KW - Helicases

KW - UvrD

U2 - 10.1111/febs.14798

DO - 10.1111/febs.14798

M3 - Journal article

C2 - 30821905

AN - SCOPUS:85063470142

SN - 1742-464X

JO - F E B S Journal

JF - F E B S Journal

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