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 - Structure of the hexameric HerA ATPase reveals a mechanism of translocation-coupled DNA-end processing in archaea
AU - Rzechorzek, Neil J.
AU - Blackwood, John K.
AU - Bray, Sian M.
AU - Maman, Joseph D.
AU - Pellegrini, Luca
AU - Robinson, Nicholas P.
PY - 2014/11/25
Y1 - 2014/11/25
N2 - The HerA ATPase cooperates with the NurA nuclease and the Mre11-Rad50 complex for the repair of double-strand DNA breaks in thermophilic archaea. Here we extend our structural knowledge of this minimal end-resection apparatus by presenting the first crystal structure of hexameric HerA. The full-length structure visualizes at atomic resolution the N-terminal HerA-ATP synthase domain and a conserved C-terminal extension, which acts as a physical brace between adjacent protomers. The brace also interacts in trans with nucleotide-binding residues of the neighbouring subunit. Our observations support a model in which the coaxial interaction of the HerA ring with the toroidal NurA dimer generates a continuous channel traversing the complex. HerA-driven translocation would propel the DNA towards the narrow annulus of NurA, leading to duplex melting and nucleolytic digestion. This system differs substantially from the bacterial end-resection paradigms. Our findings suggest a novel mode of DNA-end processing by this integrated archaeal helicase-nuclease machine.
AB - The HerA ATPase cooperates with the NurA nuclease and the Mre11-Rad50 complex for the repair of double-strand DNA breaks in thermophilic archaea. Here we extend our structural knowledge of this minimal end-resection apparatus by presenting the first crystal structure of hexameric HerA. The full-length structure visualizes at atomic resolution the N-terminal HerA-ATP synthase domain and a conserved C-terminal extension, which acts as a physical brace between adjacent protomers. The brace also interacts in trans with nucleotide-binding residues of the neighbouring subunit. Our observations support a model in which the coaxial interaction of the HerA ring with the toroidal NurA dimer generates a continuous channel traversing the complex. HerA-driven translocation would propel the DNA towards the narrow annulus of NurA, leading to duplex melting and nucleolytic digestion. This system differs substantially from the bacterial end-resection paradigms. Our findings suggest a novel mode of DNA-end processing by this integrated archaeal helicase-nuclease machine.
KW - Adenosine Triphosphatases
KW - Amino Acid Sequence
KW - Archaea
KW - Archaeal Proteins
KW - DNA Breaks, Double-Stranded
KW - DNA, Archaeal
KW - Deoxyribonucleases
KW - Models, Molecular
KW - Molecular Sequence Data
KW - Sequence Alignment
KW - Translocation, Genetic
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/ncomms6506
DO - 10.1038/ncomms6506
M3 - Journal article
C2 - 25420454
VL - 5
SP - 5506
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
ER -