7N3Z

Crystal Structure of Saccharomyces cerevisiae Apn2 Catalytic Domain

Summary for 7N3Z

• Entry DOI: 10.2210/pdb7n3z/pdb
• Related: 7N3Y
• Descriptor: DNA-(apurinic or apyrimidinic site) endonuclease 2, MAGNESIUM ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: nuclease, dna repair, eep fold, ape2 homolog, hydrolase
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Total number of polymer chains: 1
• Total formula weight: 47445.89

Authors

Wojtaszek, J.L.,Wallace, B.D.,Williams, R.S. (deposition date: 2021-06-02, release date: 2022-09-28, Last modification date: 2023-10-18)

Primary citation

Williams, J.S.,Wojtaszek, J.L.,Appel, D.C.,Krahn, J.,Wallace, B.D.,Walsh, E.,Kunkel, T.A.,Williams, R.S.
Molecular basis for processing of topoisomerase 1-triggered DNA damage by Apn2/APE2.
Cell Rep, 41:111448-111448, 2022

PubMed Abstract: Topoisomerase 1 (Top1) incises DNA containing ribonucleotides to generate complex DNA lesions that are resolved by APE2 (Apn2 in yeast). How Apn2 engages and processes this DNA damage is unclear. Here, we report X-ray crystal structures and biochemical analysis of Apn2-DNA complexes to demonstrate how Apn2 frays and cleaves 3' DNA termini via a wedging mechanism that facilitates 1-6 nucleotide endonucleolytic cleavages. APN2 deletion and DNA-wedge mutant Saccharomyces cerevisiae strains display mutator phenotypes, cell growth defects, and sensitivity to genotoxic stress in a ribonucleotide excision repair (RER)-defective background harboring a high density of Top1-incised ribonucleotides. Our data implicate a wedge-and-cut mechanism underpinning the broad-specificity Apn2 nuclease activity that mitigates mutagenic and genome instability phenotypes caused by Top1 incision at genomic ribonucleotides incorporated by DNA polymerase epsilon.

PubMed: 36198268
DOI: 10.1016/j.celrep.2022.111448

Experimental method

X-RAY DIFFRACTION (1.99 Å)