title: Radiation-induced telomere length variations in normal and in Nijmegen Breakage Syndrome cells.
abstract: OBJECTIVE
  The meiotic recombination protein 11 (MRE11), radiation sensitive 50 (RAD50) and nibrin (NBN) are members of the MRE11/RAD50/NBN (MRN) complex which plays a fundamental role in the double-strand break damage response, including DNA damage sensing, signalling and repair after exposure to ionizing radiations. In addition the MRN complex is involved in the mechanisms regulating telomere length maintenance. Based on our previous results indicating that, in contrast to X-rays, high linear energy transfer (LET) radiations were able to elongate telomeres, we investigated the behavior of cells mutated in components of the MRN complex after exposure either to 62 MeV carbon-ions (50 keV/μm, at cell surface) or X-rays.
  
  
  METHODS
  Epstein Barr Virus (EBV)-transformed lymphoblastoid cell lines (LCL) established from normal, heterozygous for the NBN gene, homozygous for either mutant/deleted NBN, RAD50 or ataxia telangiectasia mutated (ATM) genes were irradiated with 4 Gy, with telomere length being evaluated 24 h later or in time course-experiments up to 15 days later. The induction of telomeric sister chromatid exchanges (T-SCE) was measured as a hallmark of homologous directed recombinational repair.
  
  
  RESULTS
  NBN and RAD50 mutated cells failed to elongate telomeres that instead occurred in the remaining cell lines as a response only to high-LET irradiation. Also, a kinetic study with 0.5-4 Gy up to 15 days from irradiation confirmed that NBN gene was indispensable for telomere elongation. Furthermore, such an elongation, was accompanied by an increased frequency of sister chromatid exchanges at telomeres (T-SCE). In contrast, the induction of genomic sister chromatid exchanges (G-SCE) occurred for carbon-ions irrespective of NBN gene status.
  
  
  CONCLUSIONS
  We speculate that the MRN is necessary to process a subclass of high-LET radiation-induced complex DNA damage through a recombinational-repair mediated mechanism which in turn is responsible for telomere elongation.
authors.affiliation: Department of Science, University of Rome , 'Roma Tre', Rome.
authors.forename: Francesco
authors.initials: F
authors.lastname: Berardinelli
authors.forename: Antonellla
authors.initials: A
authors.lastname: Sgura
authors.forename: Alessandra
authors.initials: A
authors.lastname: Di Masi
authors.forename: Stefano
authors.initials: S
authors.lastname: Leone
authors.forename: Giuseppe A Pablo
authors.initials: GA
authors.lastname: Cirrone
authors.forename: Francesco
authors.initials: F
authors.lastname: Romano
authors.forename: Caterina
authors.initials: C
authors.lastname: Tanzarella
authors.forename: Antonio
authors.initials: A
authors.lastname: Antoccia
mesh_terms: D017766:Acid Anhydride Hydrolases; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects*; D000076228:MRE11 Homologue Protein; D049932:Nijmegen Breakage Syndrome / Q000473:pathology* / Q000503:physiopathology*; D059505:Telomere Homeostasis / Q000528:radiation effects*
chemical_list: D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes