Functional Role of NBS1 in Radiation Damage Response and Translesion DNA Synthesis
AbstractNijmegen 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. View Full-Text
Share & Cite This Article
Saito, Y.; Komatsu, K. Functional Role of NBS1 in Radiation Damage Response and Translesion DNA Synthesis. Biomolecules 2015, 5, 1990-2002.
Saito Y, Komatsu K. Functional Role of NBS1 in Radiation Damage Response and Translesion DNA Synthesis. Biomolecules. 2015; 5(3):1990-2002.Chicago/Turabian Style
Saito, Yuichiro; Komatsu, Kenshi. 2015. "Functional Role of NBS1 in Radiation Damage Response and Translesion DNA Synthesis." Biomolecules 5, no. 3: 1990-2002.