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Biomolecules 2015, 5(3), 1990-2002; doi:10.3390/biom5031990

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

Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, Japan
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Academic Editors: Fumio Hanaoka, Wolf-Dietrich Heyer and Thomas Helleday
Received: 30 June 2015 / Revised: 11 August 2015 / Accepted: 13 August 2015 / Published: 20 August 2015
(This article belongs to the Special Issue DNA Damage Response)
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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. View Full-Text
Keywords: NBS1; DNA repair; homologous recombination; chromatin remodeling; translesion DNA synthesis NBS1; DNA repair; homologous recombination; chromatin remodeling; translesion DNA synthesis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Saito, Y.; Komatsu, K. Functional Role of NBS1 in Radiation Damage Response and Translesion DNA Synthesis. Biomolecules 2015, 5, 1990-2002.

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