| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
From quantitative analysis of double-stranded DNA break (DSB) foci, we found that the RVCL-associated TREX1 mutant protein induces DSB, and that this toxicity depends on the exonuclease activity and nuclear localization of TREX1. Furthermore, we found that this DNA toxicity is unique to RVCL mutations, as it is not induced in other autoimmune disease-associated TREX1 mutants. We found that persistent expression of this RVCL mutant TREX1 in normal human fibroblasts induced cellular senescence. Furthermore, we found that cellular senescence-associated secretory phenotype (SASP) was simultaneously induced in the senescent cells induced by expression of RVCL-mutant TREX1.
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