Dual RNA 3’-end processing of H2A.X messenger RNA maintains DNA damage repair throughout the cell cycle
| Autor: | William F. Marzluff, Nick J. Proudfoot, Esther Griesbach, Margarita Schlackow |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
DNA Replication animal structures DNA Repair Science General Physics and Astronomy General Biochemistry Genetics and Molecular Biology Article Cell Line Histones 03 medical and health sciences Jurkat Cells 0302 clinical medicine Gene expression Humans Epigenetics RNA Messenger Gene RNA metabolism Messenger RNA Multidisciplinary biology Chemistry DNA damage and repair Cell Cycle RNA General Chemistry DNA HCT116 Cells Chromatin Cell biology Gene regulation 030104 developmental biology Histone H2AFX Gene Expression Regulation embryonic structures biology.protein Poly A 030217 neurology & neurosurgery DNA Damage HeLa Cells |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021) |
| ISSN: | 2041-1723 |
| Popis: | Phosphorylated H2A.X is a critical chromatin marker of DNA damage repair (DDR) in higher eukaryotes. However, H2A.X gene expression remains relatively uncharacterised. Replication-dependent (RD) histone genes generate poly(A)- mRNA encoding new histones to package DNA during replication. In contrast, replication-independent (RI) histone genes synthesise poly(A)+ mRNA throughout the cell cycle, translated into histone variants that confer specific epigenetic patterns on chromatin. Remarkably H2AFX, encoding H2A.X, is a hybrid histone gene, generating both poly(A)+ and poly(A)- mRNA isoforms. Here we report that the selective removal of either mRNA isoform reveals different effects in different cell types. In some cells, RD H2A.X poly(A)- mRNA generates sufficient histone for deposition onto DDR associated chromatin. In contrast, cells making predominantly poly(A)+ mRNA require this isoform for de novo H2A.X synthesis, required for efficient DDR. This highlights the importance of differential H2A.X mRNA 3’-end processing in the maintenance of effective DDR. H2A.X histone variant gene encodes poly(A)+ and poly(A)- mRNA isoforms which are differentially expressed depending on cell lines. Here the authors show that upon DNA damage, cells expressing more poly(A)+ isoform require this isoform for de novo H2A.X synthesis while cells with more poly(A)- isoform have sufficient H2A.X present in chromatin. |
| Databáze: | OpenAIRE |
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