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 -