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

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.

Citation

Michal R Szymanski, Wangsheng Yu, Aleksandra M Gmyrek, Mark A White, Ian J Molineux, J Ching Lee, Y Whitney Yin. A domain in human EXOG converts apoptotic endonuclease to DNA-repair exonuclease. Nature communications. 2017 May 03;8:14959

PMID: 28466855

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