title: Nijmegen breakage syndrome and DNA double strand break repair by NBS1 complex.
abstract: The isolation of the NBS1 gene revealed the molecular mechanisms of DSB repair. In response to DNA damage, histone H2AX in the vicinity of DSBs is phosphorylated by ATM. NBS1 then targets the MRE11/RAD50 complex to the sites of DSBs through interaction of the FHA/BRCT domain with gamma-H2AX. NBS1 complex binds to damaged-DNA directly, and HR repair is initiated. To collaborate DSB repair, ATM also regulates cell cycle checkpoints at G1, G2, and intra-S phases via phosphorylation of SMC, CHK2 and FANCD2. The phosphorylation of these proteins require NBS1 complex. Thus, NBS1 has at least two important roles in genome maintenance, as a DNA repair protein in HR pathway and as a signal modifier in intra-S phase checkpoints. NBS1 is also known to be involved in maintenance of telomeres, which have DSB-like structures and defects here can cause telomeric fusion. Therefore, NBS1 should be a multifunctional protein for the maintenance of genomic integrity. Further studies on NBS1 will provide insights into the mechanisms of DNA damage response and the network of these factors involved in genomic stability.
authors.affiliation: Department of Radiation Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan. shinya@hiroshima-u.ac.jp
authors.forename: Shinya
authors.initials: S
authors.lastname: Matsuura
authors.forename: Junya
authors.initials: J
authors.lastname: Kobayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tauchi
authors.forename: Kenshi
authors.initials: K
authors.lastname: Komatsu
mesh_terms: D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D013577:Syndrome
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins