Human DNA2 possesses a cryptic DNA unwinding activity that functionally integrates with BLM or WRN helicases
Abstract
Human DNA2 (hDNA2) contains both a helicase and a nuclease domain within the same polypeptide. The nuclease of hDNA2 is involved in a variety of DNA metabolic processes. Little is known about the role of the hDNA2 helicase. Using bulk and single-molecule approaches, we show that hDNA2 is a processive helicase capable of unwinding kilobases of dsDNA in length. The nuclease activity prevents the engagement of the helicase by competing for the same substrate, hence prominent DNA unwinding by hDNA2 alone can only be observed using the nuclease-deficient variant. We show that the helicase of hDNA2 functionally integrates with BLM or WRN helicases to promote dsDNA degradation by forming a heterodimeric molecular machine. This collectively suggests that the hDNA2 motor promotes the enzyme's capacity to degrade dsDNA in conjunction with BLM or WRN and thus promote the repair of broken DNA.
Article and author information
Author details
Funding
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (PP00P3 159323)
- Petr Cejka
Krebsliga Schweiz (KFS-3089-02-2013)
- Petr Cejka
European Research Council (GA 261224)
- Ralf Seidel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Antoine M van Oijen, University of Wollongong, Australia
Version history
- Received: June 7, 2016
- Accepted: September 8, 2016
- Accepted Manuscript published: September 9, 2016 (version 1)
- Version of Record published: September 20, 2016 (version 2)
Copyright
© 2016, Pinto et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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