Chromatin-associated MRN complex protects highly transcribing genes from genomic instability
| Autor: | Celine Franckhauser, Poornima Basavarajaiah, Olivier Cuvier, Rosemary Kiernan, Victor Mac, Emmanuelle Beyne, Marion Helsmoortel, David Depierre, Jérôme Déjardin, Callum Burnard, Giuseppa Grasso, Sylvie Rouquier, Xavier Contreras, Kader Salifou |
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| Přispěvatelé: | Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1) |
| Rok vydání: | 2020 |
| Předmět: |
Genome instability
DNA damage Cell Cycle Proteins [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Biology Genome Genomic Instability 03 medical and health sciences 0302 clinical medicine Gene expression Humans Molecular Biology Gene Research Articles Cancer 030304 developmental biology MRE11 Homologue Protein 0303 health sciences Multidisciplinary SciAdv r-articles Nuclear Proteins Chromatin 3. Good health Cell biology MDC1 DNA-Binding Proteins MRN complex 030217 neurology & neurosurgery Research Article DNA Damage |
| Zdroj: | Science Advances |
| Popis: | Chromatin-associated MRN protects highly transcribing genes from genomic instability. MRN-MDC1 plays a central role in the DNA damage response (DDR) and repair. Using proteomics of isolated chromatin fragments, we identified DDR factors, such as MDC1, among those highly associating with a genomic locus upon transcriptional activation. Purification of MDC1 in the absence of exogenous DNA damage revealed interactions with factors involved in gene expression and RNA processing, in addition to DDR factors. ChIP-seq showed that MRN subunits, MRE11 and NBS1, colocalized throughout the genome, notably at TSSs and bodies of actively transcribing genes, which was dependent on the RNAPII transcriptional complex rather than transcription per se. Depletion of MRN increased RNAPII abundance at MRE11/NBS1-bound genes. Prolonged MRE11 or NBS1 depletion induced single-nucleotide polymorphisms across actively transcribing MRN target genes. These data suggest that association of MRN with the transcriptional machinery constitutively scans active genes for transcription-induced DNA damage to preserve the integrity of the coding genome. |
| Databáze: | OpenAIRE |
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