Role of R-loop in antibody class switching and B cell lymphomagenesis
| Project/Area Number |
21K06015
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 43010:Molecular biology-related
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
Begum NasimAra 京都大学, 医学研究科, 特定准教授 (80362507)
|
|---|
| Project Period (FY) |
2021-04-01 – 2024-03-31
|
| Project Status |
Completed (Fiscal Year 2023)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | CSR / R-loop / AID / HNRNPU / DNA Repair / NHEJ / B Cells / Genomic Instability / B cell |
|---|
| Outline of Research at the Start |
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.
|
| Outline of Annual Research Achievements |
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.
|
Report
(3 results)
Research Products
(6 results)
