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Scientific result | Molecular mechanisms | Cellular mechanisms | DNA
An I2BC team has analyzed, at the genome scale of the yeast S.cerevisiae, the functional interactions between the Mediator of gene transcription and DNA repair proteins, reinforcing the idea that these two fundamental cellular processes are closely linked.
Transcription of DNA into messenger RNA, the first step in gene expression, and maintenance of genome integrity, which involves DNA repair mechanisms, are two functions essential for the cell. The Mediator of gene transcription is a large (1.5 MDa), conserved, multiprotein complex in eukaryotes that plays a key role in the activation and regulation of transcription by RNA polymerase II (Pol II). DNA repair involves a set of mechanisms that continuously repair DNA damages (1,000 to 1,000,000 DNA lesions per cell per day). For several years, Julie Soutourina's team has been interested in the molecular mechanisms involved in the functioning of the Mediator of the yeast Saccharomyces cerevisiae (eukaryotic model and research tool). It recently discovered a functional interaction between this complex and the nucleotide excision repair (NER) mechanism via a direct contact between the Mediator and the DNA repair protein Rad2, an endonuclease homologous to the human XPG protein (see our news on this subject).
To investigate whether other NER repair proteins interact with the Mediator, the team analyzed the genome-wide distribution of Rad26 (homologous to CSB) and Rad1-Rad10 (homologous to XPF-ERCC1), addressing the question of a potential link of these proteins to the Mediator and Pol II in yeast S. cerevisiae. Genomic analyses reveal that Rad1-Rad10 and Rad26 are present on the yeast genome in the absence of genotoxic stress, particularly in highly transcribed regions (chromatin), with Rad26 binding strongly correlated with Pol II binding. The researchers also show that Rad1-Rad10 and Rad26 are co-localized with the Mediator in intergenic regions and physically interact with this complex. Combined with multivariate analyses, these results reveal relationships between Rad1-Rad10, Rad26, the Mediator, and Pol II, modulated by changes in the dynamics of Mediator binding and transcription by Pol II.
By showing in this study that the links between the Mediator of transcription and DNA repair by NER is not limited to the Rad2 protein, but also involves Rad1-Rad10 and Rad26, the researchers provide new concepts on the functional interactions between the transcription and DNA repair machineries, relevant for some human pathologies. Contact : Julie Soutourina (email@example.com)
Diyavarshini Gopaul, Cyril Denby Wilkes, Arach Goldar, Nathalie Giordanengo Aiach, Marie-Bénédicte Barrault, Elizaveta Novikova, Julie Soutourina. Genomic analysis of Rad26 and Rad1–Rad10 reveals differences in their dependence on Mediator and RNA polymerase II. Genome Res. 2022, 32: 1516-1528 https://dx.doi.org/10.1101/gr.276371.121
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