Comparative transcriptomics reveal a novel tardigrade specific DNA binding protein induced in response to ionizing radiation

• Main Authors: Anoud, M., Delagoutte, Emmanuelle, Helleu, Quentin, Brion, A., Duvernois-Berthet, Evelyne, As, M., Marques, X., Lamribet, K., Senamaud, C., Jourdren, L., Adrait, A., Heinrich, S., Toutirais, G., Hamlaoui, S., Gropplero, G., Giovannini, I., Ponger, L., Gèze, M., Blugeon, C., Coute, Y., Guidetti, R., Rebecchi, L, Giovannangeli, C., de Cian, A., Concordet, J-P.
• Other Authors: Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Muséum national d'Histoire naturelle (MNHN), Physiologie moléculaire et adaptation (PhyMA), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Etude de la dynamique des protéomes (EDyP), Laboratoire Biosciences et bioingénierie pour la santé (BGE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), CurieCoreTech-Experimental Radiotherapy (RadeXp), Institut Curie Paris, Molécules de Communication et Adaptation des Micro-organismes (MCAM), Macromolécules et Microsystèmes en Biologie et en Médecine Institut Curie (MMBM), Laboratoire Physico-Chimie Curie Institut Curie (PCC), Institut Curie Paris -Institut de Chimie - CNRS Chimie (INC-CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie Paris -Institut de Chimie - CNRS Chimie (INC-CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), National Biodiversity Future Center (NBFC), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2024
• Subjects: [SDV]Life Sciences [q-bio]; Acutuncus antarcticus; Antarc*; antarcticus; Tardigrade
• Online Access: https://mnhn.hal.science/mnhn-04286192; https://mnhn.hal.science/mnhn-04286192/document; https://mnhn.hal.science/mnhn-04286192/file/AnoudEtAl2023.pdf; https://doi.org/10.7554/eLife.92621.1

International audience ABSTRACT Tardigrades, microscopic animals found in virtually all ecosystems, are renowned for their remarkable ability to withstand extreme conditions. Recent studies have identified novel tardigrade specific protein families that aid in resistance to desiccation and ionizing radiation (IR). Notably, a tardigrade specific DNA binding protein called Dsup (for DNA damage suppressor) has been found to protect from X-ray damage in human cells and from hydroxyl radicals in vitro . However, Dsup has only been found in two species within the Hypsibioidea superfamily. To better understand mechanisms underlying radio-resistance in the Tardigrada phylum, we first characterized DNA damage and repair in response to IR in the model species Hypsibius exemplaris . By analysis of phosphorylated H2AX, we demonstrated the induction and repair of DNA double-strand breaks after IR exposure. Importantly, the rate of single-strand breaks induced was roughly equivalent to that in human cells, suggesting that DNA repair plays a predominant role in the remarkable radio-resistance of tardigrades. In order to identify novel tardigrade specific genes involved, we next conducted a comparative transcriptomics across three species, H. exemplaris , Acutuncus antarcticus and Paramacrobiotus fairbanksi , the latter belonging to the Macrobiotoidea superfamily known to lack Dsup homologs. In all three species, many genes of DNA repair were among the most strongly overexpressed genes alongside a novel tardigrade specific gene, named T ardigrade D NA damage R esponse protein 1 (TDR1). We found that TDR1 protein interacts with DNA and forms aggregates at high concentration suggesting it may condensate DNA and act by preserving chromosome organization until DNA repair is accomplished. Remarkably, when expressed in human cells, TDR1 improved resistance to Bleomycin, a radiomimetic drug. Based on these findings, we propose that TDR1 is a novel tardigrade specific gene responsible for conferring resistance to IR. Our study sheds ...