Crystal structures of the structure-selective nuclease Mus81-Eme1 bound to flap DNA substrates
| Autor: | Kyeong Sik Jin, Jong-Bong Lee, Kyuwon Baek, Yunje Cho, Youngchang Kim, Aera Jo, Gwang Hyeon Gwon, Yaoyao Fu |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular 5' Flanking Region DNA repair Flap structure-specific endonuclease 1 Crystallography X-Ray General Biochemistry Genetics and Molecular Biology Substrate Specificity Structure-Activity Relationship Endonuclease chemistry.chemical_compound Protein structure Humans DNA Breaks Single-Stranded Protein Structure Quaternary Molecular Biology Nuclease Endodeoxyribonucleases General Immunology and Microbiology biology General Neuroscience DNA Articles Endonucleases Molecular biology DNA-Binding Proteins chemistry biology.protein Biophysics Nucleic Acid Conformation Interstrand cross-link repair Homologous recombination Protein Binding |
| Zdroj: | The EMBO Journal. 33:1061-1072 |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.1002/embj.201487820 |
| Popis: | The Mus81-Eme1 complex is a structure-selective endonuclease with a critical role in the resolution of recombination intermediates during DNA repair after interstrand cross-links, replication fork collapse, or double-strand breaks. To explain the molecular basis of 3′ flap substrate recognition and cleavage mechanism by Mus81-Eme1, we determined crystal structures of human Mus81-Eme1 bound to various flap DNA substrates. Mus81-Eme1 undergoes gross substrate-induced conformational changes that reveal two key features: (i) a hydrophobic wedge of Mus81 that separates pre- and post-nick duplex DNA and (ii) a “5′ end binding pocket” that hosts the 5′ nicked end of post-nick DNA. These features are crucial for comprehensive protein-DNA interaction, sharp bending of the 3′ flap DNA substrate, and incision strand placement at the active site. While Mus81-Eme1 unexpectedly shares several common features with members of the 5′ flap nuclease family, the combined structural, biochemical, and biophysical analyses explain why Mus81-Eme1 preferentially cleaves 3′ flap DNA substrates with 5′ nicked ends. |
| Databáze: | OpenAIRE |
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