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

Michal R. Szymanski, Wangsheng Yu, Aleksandra M. Gmyrek, Mark White, Ian J. Molineux, J. Ching Lee, Yuhui Yin

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Human EXOG (hEXOG) is a 50-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 1.85Å 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.

Original languageEnglish (US)
Article number14959
JournalNature Communications
Volume8
DOIs
StatePublished - Jan 1 2017

Fingerprint

Endonucleases
Exonucleases
deoxyribonucleic acid
DNA
Substrates
DNA-Directed DNA Polymerase
Mitochondrial DNA
Tapes
Phosphodiesterase I
nuclease
Repair
DNA Repair
wings
tapes
Enzymes
enzymes
Catalytic Domain
correxonuclease
synthesis

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

A domain in human EXOG converts apoptotic endonuclease to DNA-repair exonuclease. / Szymanski, Michal R.; Yu, Wangsheng; Gmyrek, Aleksandra M.; White, Mark; Molineux, Ian J.; Lee, J. Ching; Yin, Yuhui.

In: Nature Communications, Vol. 8, 14959, 01.01.2017.

Research output: Contribution to journalArticle

Szymanski, Michal R. ; Yu, Wangsheng ; Gmyrek, Aleksandra M. ; White, Mark ; Molineux, Ian J. ; Lee, J. Ching ; Yin, Yuhui. / A domain in human EXOG converts apoptotic endonuclease to DNA-repair exonuclease. In: Nature Communications. 2017 ; Vol. 8.
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