Molecular mechanism of partner choice for recombination by two RecA homologs
Project/Area Number |
16H04742
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Molecular biology
|
Research Institution | Osaka University |
Principal Investigator |
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
|
Keywords | 相同組換え / RAD51 / 減数分裂 / DNA修復 / ゲノム安定化 / DMC1 / 染色体 / 組換え / がん / Rad51 / Dmc1 / RecAホモログ / パートナー選択 / 相同鎖検索 |
Outline of Final Research Achievements |
Homologous recombination is essential for the maintenance of genome stability. RAD51 assembly on single-stranded (ss)DNAs is a crucial step in the recombination-dependent repair of DNA damage. The formation of the RAD51 filament is promoted by various RAD51-interacting proteins including RAD51 paralogues. However, the mechanisms underlying the differential control of RAD51 filament dynamics by these factors remain largely unknown. In this study, we report a new role for the human RAD51 paralog, SWSAP1, as a novel regulator of RAD51 assembly and disassembly. Swsap1-deficient cells show defects in DNA damage-induced RAD51 assembly during both mitosis and meiosis. Defective RAD51 assembly in SWSAP1-depleted cells is suppressed by the depletion of FIGNL1, which binds to RAD51 as well as SWSAP1. Purified FIGNL1 promotes the dissociation of RAD51 from ssDNAs. Taken together, our data suggest that SWSAP1 protects RAD51 filaments by antagonizing the anti-recombinase, FIGNL1.
|
Academic Significance and Societal Importance of the Research Achievements |
本研究成果は相同組換えのアクセル役のSWSAP1と連携して機能する、ブレーキ役の新規タンパク質・遺伝子タンパク質・遺伝子(FIGNL1)を発見しました。SWSAP1, FIGNL1の2者のタンパク質の機能を明らかにすることで、生体内でのDNA同士の交換反応である相同組換えを適切に制御するメカニズムを解明しました。相同組換えの機能不全による発ガン率の上昇の原因解明や診断・治療方法の開発につながることが期待できます。また、今回発見した組換え因子を人工的に制御する技術の開発を通して、不妊の治療、ゲノム編集を介した遺伝子治療(置き換え)の最適化など幅広い貢献が期待できます。
|
Report
(4 results)
Research Products
(49 results)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] A. Shinohara, Human RAD51 paralogue, SWSAP1, fosters RAD51 filament by regulating the anti-recombinase, FIGNL1 AAA+ ATPase.2019
Author(s)
Matsuzaki, K., Kondo, S., Ishikawa, T., and A. Shinohara,
-
Journal Title
Nature Communications
Volume: 10
Issue: 1
Pages: 1407-1407
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
[Journal Article] Modulating crossover frequency and interference for obligate crossovers in Saccharomyces cerevisiae meiosis.2017
Author(s)
Chakrabotty, P., Ajith, VP.., Chen, K., Duttta, A., Krishnaprasad G.N., Tekkedil, M.M., Shinohara, A., Steinmetz, L. M., and Nishant, K.T.
-
Journal Title
G3(Bethesda)
Volume: 印刷中
Issue: 5
Pages: 1511-1524
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] RFTS-dependent negative regulation of Dnmt1 by nucleosome structure and histone tails.2017
Author(s)
Mishima Y, Brueckner L, Takahashi S, Kawakami T, Arita K, Oka S, Otani J, Hojo H, Shirakawa M, Shinohara A, Watanabe M, Suetake I
-
Journal Title
FEBS J.
Volume: 284
Issue: 20
Pages: 3455-3469
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] The Paf1 Complex Shapes the Landscape of Double-strand Breaks along Meiotic Chromosomes in Saccharomyces cerevisiae2016
Author(s)
Santosh, G. K., Patel, K.J., Colletti M.M., Sasanuma, H., Shinohara, M., Hochwagen, A., and A. Shinohara
-
Journal Title
Genetics
Volume: 202
Issue: 2
Pages: 497-512
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
-
[Journal Article] Chromosome synapsis alleviates Mek1-dependent suppression of meiotic DNA repair.2016
Author(s)
Subramanian, V.V., MacQueen, A. J., Vader, G., Shinohara, M., Borde, V., Shinohara, A. and A. Hochwagen
-
Journal Title
Current Biology
Volume: 14
Issue: 2
Pages: e1002369-e1002369
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-