2017 Fiscal Year Final Research Report
Dysregulation of mRNA processing in ovarian cancer
| Project/Area Number |
16H06757
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Obstetrics and gynecology
|
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| Research Institution | The University of Tokyo |
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Principal Investigator |
|
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| Project Period (FY) |
2016-08-26 – 2018-03-31
|
| Keywords | 卵巣癌 / DNA損傷修復 / 相同組換修復経路 / mRNAプロセシング / スプライシング |
|---|
| Outline of Final Research Achievements |
Whole-exome sequencing studies of malignancies detected recurrent somatic mutations in U2 snRNP components of the spliceosome. These factors was also listed as novel players of DNA damage response in several genome wide screens for DDR genes. Here we unveiled two distinct pathways how spliceosome U2 snRNP factors contribute to genome stability. The main function is indirect, through transcription, to maintain the protein levels of essential repair factors and contribute to homologous recombination repair. In addition real-time laser microirradiation analysis identified the rapid recruitment of SNRPA1 to DNA damage sites. Intensive functional analysis of SNRPA1 unveiled the other, more immediate and direct effect to process R-loop structure, deleterious transcriptional by-products for the genome, at sites of ongoing transcription.
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| Free Research Field |
婦人科腫瘍学
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