Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Structural and functional insights into DNA-end processing by the archaeal HerA helicase-NurA nuclease complex
AU - Blackwood, John K.
AU - Rzechorzek, Neil J.
AU - Abrams, Andrew S.
AU - Maman, Joseph D.
AU - Pellegrini, Luca
AU - Robinson, Nicholas P.
PY - 2012/4
Y1 - 2012/4
N2 - Helicase-nuclease systems dedicated to DNA end resection in preparation for homologous recombination (HR) are present in all kingdoms of life. In thermophilic archaea, the HerA helicase and NurA nuclease cooperate with the highly conserved Mre11 and Rad50 proteins during HR-dependent DNA repair. Here we show that HerA and NurA must interact in a complex with specific subunit stoichiometry to process DNA ends efficiently. We determine crystallographically that NurA folds in a toroidal dimer of intertwined RNaseH-like domains. The central channel of the NurA dimer is too narrow for double-stranded DNA but appears well suited to accommodate one or two strands of an unwound duplex. We map a critical interface of the complex to an exposed hydrophobic epitope of NurA abutting the active site. Based upon the presented evidence, we propose alternative mechanisms of DNA end processing by the HerA-NurA complex.
AB - Helicase-nuclease systems dedicated to DNA end resection in preparation for homologous recombination (HR) are present in all kingdoms of life. In thermophilic archaea, the HerA helicase and NurA nuclease cooperate with the highly conserved Mre11 and Rad50 proteins during HR-dependent DNA repair. Here we show that HerA and NurA must interact in a complex with specific subunit stoichiometry to process DNA ends efficiently. We determine crystallographically that NurA folds in a toroidal dimer of intertwined RNaseH-like domains. The central channel of the NurA dimer is too narrow for double-stranded DNA but appears well suited to accommodate one or two strands of an unwound duplex. We map a critical interface of the complex to an exposed hydrophobic epitope of NurA abutting the active site. Based upon the presented evidence, we propose alternative mechanisms of DNA end processing by the HerA-NurA complex.
KW - Adenosine Triphosphate
KW - Amino Acid Sequence
KW - Archaeal Proteins
KW - Conserved Sequence
KW - Crystallography, X-Ray
KW - DNA
KW - DNA Helicases
KW - Deoxyribonucleases
KW - Dimerization
KW - Models, Molecular
KW - Molecular Sequence Data
KW - Protein Folding
KW - Protein Structure, Tertiary
KW - Ribonuclease H
KW - Sulfolobus solfataricus
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1093/nar/gkr1157
DO - 10.1093/nar/gkr1157
M3 - Journal article
C2 - 22135300
VL - 40
SP - 3183
EP - 3196
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 7
ER -