A domain in human EXOG converts apoptotic endonuclease to DNA-repair exonuclease

Michal R. Szymanski, Wangsheng Yu, Aleksandra M. Gmyrek, Mark A. White, Ian J. Molineux, J. Ching Lee and Y. Whitney Yin ()
Additional contact information
Michal R. Szymanski: University of Texas Medical Branch
Wangsheng Yu: University of Texas Medical Branch
Aleksandra M. Gmyrek: University of Texas Medical Branch
Mark A. White: Sealy Center for Structural Biology, University of Texas Medical Branch
Ian J. Molineux: University of Texas at Austin
J. Ching Lee: Sealy Center for Structural Biology, University of Texas Medical Branch
Y. Whitney Yin: University of Texas Medical Branch

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract Human EXOG (hEXOG) is a 5′-exonuclease that is crucial for mitochondrial DNA repair; the enzyme belongs to a nonspecific nuclease family that includes the apoptotic endonuclease EndoG. Here we report biochemical and structural studies of hEXOG, including structures in its apo form and in a complex with DNA at 1.81 and 1.85 Å resolution, respectively. A Wing domain, absent in other ββα-Me members, suppresses endonuclease activity, but confers on hEXOG a strong 5′-dsDNA exonuclease activity that precisely excises a dinucleotide using an intrinsic ‘tape-measure’. The symmetrical apo hEXOG homodimer becomes asymmetrical upon binding to DNA, providing a structural basis for how substrate DNA bound to one active site allosterically regulates the activity of the other. These properties of hEXOG suggest a pathway for mitochondrial BER that provides an optimal substrate for subsequent gap-filling synthesis by DNA polymerase γ.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms14959 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14959

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms14959

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().