| 研究課題/領域番号 |
21K06015
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分43010:分子生物学関連
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| 研究機関 | 京都大学 |
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研究代表者 |
Begum NasimAra 京都大学, 医学研究科, 特定准教授 (80362507)
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| 研究期間 (年度) |
2021-04-01 – 2024-03-31
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| 研究課題ステータス |
完了 (2023年度)
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| 配分額 *注記 |
4,160千円 (直接経費: 3,200千円、間接経費: 960千円)
2023年度: 780千円 (直接経費: 600千円、間接経費: 180千円)
2022年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円)
2021年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円)
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| キーワード | CSR / R-loop / AID / HNRNPU / DNA Repair / NHEJ / B Cells / Genomic Instability / B cell |
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| 研究開始時の研究の概要 |
AID-induced DNA lesions in the R-loop causes recombinogenic DNA breaks in B cell genome, which oftentimes are potential source of oncogenic rearrangement This study aims to elucidate the mechanism and regulation of R-loop involved in antibody isotype switching and B cell lymphomagenesis.
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| 研究実績の概要 |
During class switching in mature B cells, maintaining genomic integrity is crucial as it involves DNA breaks and rearrangement of the antibody gene locus. This process is induced by AID expression and locus-specific transcription that generate R-loop and single-stranded complex DNA structure. This study shows that the heterogeneous ribonucleoprotein, HNRNPU, plays a crucial role in the repair-rearrangement phase following the DNA breaks at the Ig locus. HNRNPU interacts with the DNA repair factors and binds to complex DNA structures generated in the Ig locus. Loss of HNRNPU disrupts DNA repair, causing an R-loop imbalance and hindering antibody class switch processes, suggesting the HNRNPU is crucial for efficient DNA repair and immune response coordination.
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