title: Structure of the hexameric HerA ATPase reveals a mechanism of translocation-coupled DNA-end processing in archaea.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Rzechorzek
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: John K
authors.initials: JK
authors.lastname: Blackwood
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: Sian M
authors.initials: SM
authors.lastname: Bray
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Maman
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: Luca
authors.initials: L
authors.lastname: Pellegrini
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Robinson
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001105:Archaea / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D019843:Archaeal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D019641:DNA, Archaeal / Q000235:genetics* / Q000378:metabolism; D003851:Deoxyribonucleases / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014178:Translocation, Genetic
chemical_list: D019843:Archaeal Proteins; D019641:DNA, Archaeal; D003851:Deoxyribonucleases; D000251:Adenosine Triphosphatases