title: RAD50, an SMC family member with multiple roles in DNA break repair: how does ATP affect function?
abstract: The protein complex including Mre11, Rad50, and Nbs1 (MRN) functions in DNA double-strand break repair to recognize and process DNA ends as well as signal for cell cycle arrest. Amino acid sequence similarity and overall architecture make Rad50 a member of the structural maintenance of chromosome (SMC) protein family. Like SMC proteins, Rad50 function depends on ATP binding and hydrolysis. All current evidence indicates that ATP binding and hydrolysis cause architectural rearrangements in SMC protein complexes that are important for their functions in organizing DNA. In the case of the MRN complex, the functional significance of ATP binding and hydrolysis are not yet defined. Here we review the data on the ATP-dependent activities of MRN and their possible mechanistic significance. We present some speculation on the role of ATP for function of the MRN complex based on the similarities and differences in the molecular architecture of the Rad50-containing complexes and the SMC complexes condensin and cohesin.
authors.affiliation: Department of Cell Biology and Genetics, Erasmus University Medical Center, Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Eri
authors.initials: E
authors.lastname: Kinoshita
authors.forename: Eddy
authors.initials: E
authors.lastname: van der Linden
authors.forename: Humberto
authors.initials: H
authors.lastname: Sanchez
authors.forename: Claire
authors.initials: C
authors.lastname: Wyman
mesh_terms: D017766:Acid Anhydride Hydrolases; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000502:physiology; D002875:Chromosomes / Q000502:physiology* / Q000648:ultrastructure; D015825:Chromosomes, Fungal / Q000502:physiology / Q000648:ultrastructure; D053960:DNA Breaks; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000502:physiology*; D004271:DNA, Fungal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008322:Mammals; D008957:Models, Genetic; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000502:physiology*; D015003:Yeasts / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; C086930:RAD50 protein, S cerevisiae; C480032:Rad50 protein, S pombe; C118650:SMC protein, Bacteria; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D000255:Adenosine Triphosphate; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes