論文 - 詳細
| RRC ID | 76107 |
|---|---|
| 著者 | Zheleva A, Camino LP, Fernández-Fernández N, García-Rubio M, Askjaer P, García-Muse T, Aguilera A. |
| タイトル | THSC/TREX-2 deficiency causes replication stress and genome instability in Caenorhabditis elegans. |
| ジャーナル | J Cell Sci |
| Abstract |
Transcription is an essential process of DNA metabolism, yet it makes DNA more susceptible to DNA damage. THSC/TREX-2 is a conserved eukaryotic protein complex with a key role in mRNP biogenesis and maturation that prevents genome instability. One source of such instability is linked to transcription, as shown in yeast and human cells, but the underlying mechanism and whether this link is universal is still unclear. To obtain further insight into the putative role of the THSC/TREX-2 complex in genome integrity, we have used Caenorhabditis elegans mutants of the thp-1 and dss-1 components of THSC/TREX-2. These mutants show similar defective meiosis, DNA damage accumulation and activation of the DNA damage checkpoint. However, they differ from each other regarding replication defects, as determined by measuring dUTP incorporation in the germline. Interestingly, this specific thp-1 mutant phenotype can be partially rescued by overexpression of RNase H. Furthermore, both mutants show a mild increase in phosphorylation of histone H3 at Ser10 (H3S10P), a mark previously shown to be linked to DNA-RNA hybrid-mediated genome instability. These data support the view that both THSC/TREX-2 factors prevent transcription-associated DNA damage derived from DNA-RNA hybrid accumulation by separate means. |
| 巻・号 | 134(20) |
| 公開日 | 2021-10-15 |
| DOI | 10.1242/jcs.258435 |
| PII | 272263 |
| PMID | 34553761 |
| PMC | PMC10658913 |
| MeSH | Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics DNA Damage / genetics DNA Replication / genetics Exodeoxyribonucleases* / genetics Genomic Instability / genetics Humans Saccharomyces cerevisiae / metabolism Saccharomyces cerevisiae Proteins / metabolism Transcription, Genetic |
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オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm3507 tm370 |