ダウンロード数: 396
このアイテムのファイル:
ファイル | 記述 | サイズ | フォーマット | |
---|---|---|---|---|
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 |
このリポジトリに保管されているアイテムはすべて著作権により保護されています。