Functional Role of NBS1 in Radiation Damage Response and Translesion DNA Synthesis

• Published in: Biomolecules 2015-08, Vol.5 (3), p.1990-2002
• Main Authors: Saito, Yuichiro, Komatsu, Kenshi
• Format: Article
• Language: English
• Subjects: Animals; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - metabolism; Chromatin Assembly and Disassembly - drug effects; Chromatin Assembly and Disassembly - radiation effects; chromatin remodeling; DNA - biosynthesis; DNA - chemistry; DNA - genetics; DNA Damage; DNA repair; homologous recombination; Homologous Recombination - drug effects; Homologous Recombination - radiation effects; Humans; NBS1; Nuclear Proteins - chemistry; Nuclear Proteins - metabolism; Radiation; Review; translesion DNA synthesis
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom5031990

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.