title: Functional Role of NBS1 in Radiation Damage Response and Translesion DNA Synthesis.
abstract: Nijmegen breakage syndrome (NBS) is a recessive genetic disorder characterized by increased sensitivity to ionizing radiation (IR) and a high frequency of malignancies. NBS1, a product of the mutated gene in NBS, contains several protein interaction domains in the N-terminus and C-terminus. The C-terminus of NBS1 is essential for interactions with MRE11, a homologous recombination repair nuclease, and ATM, a key player in signal transduction after the generation of DNA double-strand breaks (DSBs), which is induced by IR. Moreover, NBS1 regulates chromatin remodeling during DSB repair by histone H2B ubiquitination through binding to RNF20 at the C-terminus. Thus, NBS1 is considered as the first protein to be recruited to DSB sites, wherein it acts as a sensor or mediator of DSB damage responses. In addition to DSB response, we showed that NBS1 initiates Polη-dependent translesion DNA synthesis by recruiting RAD18 through its binding at the NBS1 C-terminus after UV exposure, and it also functions after the generation of interstrand crosslink DNA damage. Thus, NBS1 has multifunctional roles in response to DNA damage from a variety of genotoxic agents, including IR.
authors: Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, Japan. yu_saito@house.rbc.kyoto-u.ac.jp.
authors: Yuichiro
authors: Y
authors: Saito
authors: Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, Japan. komatsu@house.rbc.kyoto-u.ac.jp.
authors: Kenshi
authors: K
authors: Komatsu
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects / Q000528:radiation effects; D004247:DNA / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D004249:DNA Damage; D059765:Homologous Recombination / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D011827:Radiation
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D004247:DNA
keywords: DNA repair; NBS1; chromatin remodeling; homologous recombination; translesion DNA synthesis