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ファイル | 記述 | サイズ | フォーマット | |
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j.issn.2218-676X.2013.04.05.pdf | 1.03 MB | Adobe PDF | 見る/開く |
タイトル: | Role of NBS1 in DNA damage response and its relationship with cancer development |
著者: | Saito, Yuichiro Fujimoto, Hiroko Kobayashi, Junya |
著者名の別形: | 小林, 純也 |
キーワード: | NBS1 ataxia telangiectasia mutated (ATM) cell cycle checkpoint homologous recombination (HR) translesion DNA synthesis (TLS) |
発行日: | Jun-2013 |
出版者: | Pioneer Bioscience Publishing Company |
誌名: | Translational Cancer Research |
巻: | 2 |
号: | 3 |
開始ページ: | 178 |
終了ページ: | 189 |
抄録: | 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. |
著作権等: | © Pioneer Bioscience Publishing Company. |
URI: | http://hdl.handle.net/2433/176337 |
DOI(出版社版): | 10.3978/j.issn.2218-676X.2013.04.05 |
出現コレクション: | 学術雑誌掲載論文等 |
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