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Role of NBS1 in DNA damage response and its relationship with cancer development

   
@article{TCR1097,
	author = {Yuichiro Saito and Hiroko Fujimoto and Junya Kobayashi},
	title = {Role of NBS1 in DNA damage response and its relationship with cancer development},
	journal = {Translational Cancer Research},
	volume = {2},
	number = {3},
	year = {2013},
	keywords = {},
	abstract = {Nijmegen breakage syndrome (NBS) is a recessive genetic disorder characterized by an elevated sensitivity to ionizing radiation, chromosome instability, and a high frequency of malignancies phenotypes similar to those of ataxia-telangiectasia (A-T). NBS1, the product of the causative gene in NBS, contains several protein-interaction motifs in the N-terminus and C-terminus. The N-terminal FHA/BRCT domains interact with MDC1, γ-H2AX, TopBP1, and WRN, and the C-terminal motifs are indispensable for binding MRE11, ataxia telangiectasia mutated (ATM), RAD18, and RNF20. NBS1 typically forms a complex with the hMRE11/hRAD50 nuclease and functions in homologous recombination repair for DNA double-strand breaks (DSBs). The interactions of NBS1 with ATM, MDC1, γ-H2AX, and TopBP1 are important for focus formation at the sites of DSB and the activation of the ATM/ATR-dependent cell cycle checkpoint following DNA damage. NBS1 also participates in the regulation of RAD18/Polη-dependent translesion DNA synthesis (TLS) through its interaction with RAD18 and WRN. Recently, the ATM/ATR-dependent checkpoints have been reported to function as an anti-cancer barrier in human tumorigenesis. As NBS1 is an important factor in the regulation of ATM/ATR activation, a relationship between NBS1 and cancer development is probable. In fact, some studies have shown an association between several single-nucleotide polymorphisms (SNPs) or mutations in the N-terminus of NBS1 and the risk of lymphoma or breast cancer. However, the contribution of C-terminal SNPs or mutations to cancer development has not yet been reported. Therefore, further studies of the C-terminus are required to clarify the role of NBS1 in cancer development.},
	issn = {2219-6803},	url = {https://tcr.amegroups.org/article/view/1097}
}