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

Biomolecules

Yuichiro Saito¹  Kenshi Komatsu²  Fumio Hanaoka²  Wolf-Dietrich Heyer² 

[1] Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, Japan; E-Mail

关键词: NBS1;    DNA repair;    homologous recombination;    chromatin remodeling;    translesion DNA synthesis;   

DOI  :  10.3390/biom5031990

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.