Mycobacterium tuberculosis UvrD1 and UvrD2 helicases unwind G-quadruplex DNA

Saha, Tias and Shukla, Kaustubh and Thakur, Roshan Singh and Desingu, Ambika and Nagaraju, Ganesh (2019) Mycobacterium tuberculosis UvrD1 and UvrD2 helicases unwind G-quadruplex DNA. In: FEBS JOURNAL, 286 (11). pp. 2062-2086.

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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.

Item Type:	Journal Article
Publication:	FEBS JOURNAL
Publisher:	WILEY
Additional Information:	copyright for this article is belongs to WILEY
Keywords:	DNA replication and genome stability; G4 DNA; Helicases; UvrD
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	26 Jul 2019 06:49
Last Modified:	26 Jul 2019 06:49
URI:	http://eprints.iisc.ac.in/id/eprint/63141

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