Loop extrusion as a mechanism for DNA Double-Strand Breaks repair foci formation
| Autor: | Thomas Clouaire, Emiliano P. Ricci, Pierre Caron, Daan Noordermeer, Philippe E. Mangeot, Gaëlle Legube, Coline Arnould, Raphaël Mourad, Rocher |
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| Přispěvatelé: | Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cohesin
0303 health sciences DNA Double-Strand Breaks DNA damage DNA repair 030302 biochemistry & molecular biology [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Loop extrusion Chromatin Cell biology 03 medical and health sciences chemistry.chemical_compound chemistry Transcription (biology) Topologically Associated Domains Nucleosome DNA Damage Response biological phenomena cell phenomena and immunity H2AX DNA 030304 developmental biology Genomic organization |
| Popis: | DNA Double-Strand Breaks (DSBs) repair is essential to safeguard genome integrity. Upon DSBs, the ATM PI3K kinase rapidly triggers the establishment of megabase-sized, γH2AX-decorated chromatin domains which further act as seeds for the formation of DNA Damage Response (DDR) foci1. How these foci are rapidly assembled in order to establish a “repair-prone” environment within the nucleus is yet unclear. Topologically Associating Domains (TADs) are a key feature of 3D genome organization that regulate transcription and replication, but little is known about their contribution to DNA repair processes2,3. Here we found that TADs are functional units of the DDR, instrumental for the correct establishment of γH2AX/53BP1 chromatin domains in a manner that involves one-sided cohesin-mediated loop extrusion on both sides of the DSB. We propose a model whereby H2AX-containing nucleosomes are rapidly phosphorylated as they actively pass by DSB-anchored cohesin. Our work highlights the critical impact of chromosome conformation in the maintenance of genome integrity and provides the first example of a chromatin modification established by loop extrusion. |
| Databáze: | OpenAIRE |
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