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

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 ???-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 ?.

SUBMITTER: Szymanski MR

PROVIDER: S-EPMC5418593 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Szymanski Michal R MR Yu Wangsheng W Gmyrek Aleksandra M AM White Mark A MA Molineux Ian J IJ Lee J Ching JC Yin Y Whitney YW

Nature communications 20170503

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 p ...[more]

PMID: 28466855

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