Demography and adaptation are important factors determining the evolution of plant species. Many plant species are substructured into populations or demes connected by migration (metapopulations). The spatial distribution of populations and migration patterns depend on the means of dispersal. Since plants are sessile organisms, they also have to cope with both biotic and abiotic stresses. Therefore adaptations to local environmental conditions are essential to ensure survival and duration of the species. Wild tomato species (Solanum section Lycopersicon) are native to western South America. They occur in diverse and often extreme habitats including rain forests, coastal regions, high altitude habitats in the Andean Mountains and also hyperarid deserts in the Atacama Desert. Therefore, wild tomatoes are a good model system to study plant evolution and genomic bases for plant adaptation. This study focuses on the wild tomato species Solanum chilense, which exhibits a metapopulation structure with populations distributed from southern Peru to northern Chile. In its native range, S. chilense is confronted with different abiotic stresses including drought, cold and salinity. I sequenced 30 unlinked nuclear genes from 23 populations using next generation sequencing. 16 genes are involved in the abiotic stress response and serve as candidates for selection and adaptation. The remaining 14 genes are used as references to study the genomic average and species past demography. In the first part of this study, I investigated the demographic history of the wild tomato species Solanum chilense. Genetic data analyses revealed a north-south cline. This cline includes 1) a decrease of genetic variation from north to south, 2) an increase in the strength of population expansion along the cline, and 3) an increase in genetic differentiation from other wild tomato species towards the south of the range. Results further revealed that the populations form four groups: a central group and three peripheral groups. Altogether the results suggest that S. chilense originated in the northern part of its current distribution and migrated to the south, via two routes, along the coast and higher up in the Andes. During this north-south colonization, at least three bottlenecks occurred. In the second part of this study, I investigated natural selection and local adaptation in S. chilense. Signatures of selection and local adaptation were detected in the abiotic stress-related genes, for example signatures of positive selection in high altitude populations were found possibly indicating adaptation to low temperatures. Interestingly, signatures of balancing selection were detected as well in high altitude populations reflecting probable adaptation to different types of abiotic stresses. The coastal populations showed a distinct pattern. Several genes involved in the salt stress response exhibited signatures of local adaptation. Performing a salt stress experiment, I revealed that low altitude populations cope better with such stress than populations from intermediate or high altitudes. The coastal populations also showed an accumulation of nonsynonymous and possibly deleterious genetic variation, which can be explained by extreme bottlenecks and potential occurrence of selfing in some populations. Signatures of selection and local adaptation in S. chilense were mainly detected in populations from the peripheral groups and not in the central region, in agreement with the hypothesis that local adaptation is associated with the colonization of new territories. In summary, this study showed that demography plays an important role in the evolutionary history of S. chilense and that local adaptation for key abiotic stresses occurs more frequently in the marginal ranges of the species distribution.

No description available.

No description available.

In this dissertation project comparative morphological studies on the nervous system, mandible structure and sensory equipment of Decapoda and Peracarida are presented and interpreted with regard to the evolution of the taxa. This is a cumulative dissertation and the results were obtained in several separate publications. Both larval and adult characters as well as the ontogeny of certain features were included and analysed using various sets of imaging techniques ranging from conventional light microscopy to ultrastructure research with transmission electron microscopy. Attention was focused on the description and development of previously unexplored sets of characters which can be included in a reconstruction of crustacean phylogeny. The adult nervous system in Decapoda has been extensively studied for a long time and shows very specific taxon generic adaptations. In the present thesis now also the larval nervous system was comparatively investigated in its entirety for the first time. By use of computer assisted 3D reconstruction general and species specific features were analysed and basic elements were described, including the segmental ganglia and their neuropils as well as the segmental nerves. The larval nervous system is in a transitory stage to the adult organization, already showing well differentiated basic elements. Likewise the phase-specific structure reflects adaptations to larval life. The studied species respectively represent one of the three decapod main lineages, i.e. Caridea, Anomura and Brachyura. Against this background variations in the differentiation of 3certain ganglia can best be explained with shifts in the timing of morphogenetic events, i.e. heterochrony. The studies on heterochrony as motors of evolution are another core topic of this project. Along with the latter study also the morphology and finestructure of decapod mandibles during larval development was investigated, based on two closely related species, showing different feeding modes in the zoea I. Thus, it could be tested whether the mandible structure in early larval stages only depends on feeding modes or an evolutionary ground pattern is recognizable even in species with non-feeding zoea I. In case of a comparison of mandibles, restricted only to the features of the zoea I, adaptations to food preferences may obscure taxon- specific features. In detailed inspection, however, it could be shown that even in species with non- feeding zoea I apomorph basic features of the related taxon can be recognized. This supports the hypothesis of the presence of phylogenetic relevant character sets in larval mandible morphology. The monophyly of the Mandibulata is manly based on hypotheses defending the homology of the mandibles in Myriapoda, Hexapoda and Crustacea, nevertheless, knowledge on sensory structures located on the gnathal lobe is astonishingly limited, even less is known about their ultrastructure. The development of this complex of characteristics represents a further aim of this project. For this purpose the ultrastructure of the mandibular gnathal lobe of the zoea I of a rockpool prawn was analysed. Besides external structure and location and an analysis of the modality specific structures, special attention was paid to the features of the lacinia mobilis. In total a number of seven different types of sensilla, innervated by four different types of dendrites, could be described and compared, including (1) mechanoreceptive hair-sensilla and (2) putative contact-chemo-receptors, as well as (3) sensilla without external structures and (4) sensilla associated with inflexible spines. The results reveal new insights into the functional morphology of larval decapod mandibles and constitute a significant character complex including fine- and ultrastructural features. Following-up the character complex was completed by investigations of respective features of a peracarid representative. The results also present an overview of the sensory elements of the mandible as well as a detailed analysis of the lacinia mobilis based on their ultrastructure and features related to ecdysis. By comparison it can be shown, that the lacinia mobilis on the right mandible in Peracarida and also the respective structure in Decapoda are mechanosensitive sensilla. In conclusion the hypothesis of a possible homology of the latter structures gains further support. Concerning the structures on the left mandible a differentiated consideration is necessary. No unambiguous conclusions can be made and it remains to be resolved if the lacinia mobilis on the left mandible is a derived sensillum or a compound structure equipped with multiple sensilla. With the application of many different state-of-the-art technics and the overall discussion of the results an important contribution to eumalacostracan phylogeny, maybe even crustacean phylogeny, could be made. Character sets comprising different levels of organization of the arthropod body could be established. Primarily phylogenetic relevant signal in the basic elements of the larval nervous system and the mandibles in Decapoda could be presented. Furthermore, highly complex and detailed character sets of the mandible ultrastructure were developed, revealing a comprehensive presentation of the sensory capacities of eumalacostracan mandibles and by comparison already allowed conclusions about the homology of the lacinia mobilis. Thus, also the phylogenetic position of the respective taxa can be confirmed.

No description available.

Die als Zehnfußkrebse oder auch als Decapoda bezeichneten Arthropoden sind eine weltweit verbreitete, zum Teil hoch spezialisierte und vielseitig angepasste Gruppe, die in fast allen aquatischen Ökosystemen, aber auch in terrestrischen Habitaten zu finden ist. Die enorme Artenzahl von 17,635 rezent und fossil bekannten Arten (De Grave et al., 2009) sowie das hohe Alter der Gruppe an sich erschwert die systematische Eingliederung einzelner Arten. Fossile Funde von Dekapoden wurden bis ins Devon (vor 415 bis 359,2 Millionen Jahren) datiert (Schram et al., 1978). Damit haben die rezenten Vertreter viele Millionen Jahre Evolution durchlaufen und die Ergebnisse dieses langwierigen Prozesses schlagen sich in einer hohen morphologischen Vielfalt zwischen den Arten nieder. Um eine zuverlässige Phylogenie aufstellen und Arten eindeutig charakterisieren zu können sind neue Merkmale, Methoden und Ansätze erforderlich. Eine zuverlässige Bestimmung und Einordnung der verschiedenen Arten bildet die Basis für verschiedene Datenbanken und Projekte wie z.B. GenBank, Barcoding of Life (BOLD), German Barcode of Life (GBOL) oder Barcoding Fauna Bavarica und zeigt, welch hohen Stellenwert die Taxonomie besitzt. Ziel dieser kumulativen Dissertation ist es mit Einsatz von verschiedenen modernen morphologischen und molekularen Methoden wie der Rasterelektronenmikroskopie, der Fluoreszenzmikroskopie und der Analyse von mitochondrialen DNA-Sequenzen (Cytochrom-c-Oxydase) neue Merkmalssätze zur besseren Charakterisierung der verschiedenen Arten und deren Artabgrenzungen zu erarbeiten. Aber auch klassische Methoden wie das Abwägen von morphologischen Merkmalen, kommen in einem integrativen Ansatz zur Artabgrenzung zur Anwendung. Die in den Arbeiten angewandte Rasterelektronenmikroskopie erlaubt eine weitaus höhere Vergrößerung als die klassische Lichtmikroskopie bei gleichzeitig höherer Auflösung und Schärfentiefe. Somit konnten auch kleinste eidonomische (Bestimmungs-) Merkmale wie das Dorsalorgan oder einzelne Setae-Typen bei Zoea-Larven detailliert beschrieben und als neue oder früher wenig beachtete morphologischen Merkmale zur systematischen Einordnung herangezogen werden (Publikationen I, II und III). Des Weiteren konnte mit Hilfe der Fluoreszenzmikroskopie anhand von DAPI-Färbungen gezeigt werden, dass die Anordnung der Zellkerne von Zoea-Larven aus den verschiedenen Unterordnungen Caridea, Anomura und Brachyura charakteristische Muster aufweist. Dieses Kriterium wird als möglicher Merkmalssatz in der Taxonomie diskutiert (Publikation VI). Ein weiteres Feld der modernen Taxonomie wird durch Publikation V abgedeckt: molekulare Analysen auf der Basis des mitochondrialen proteincodierenden Genes COI (cytochrome oxidase subunit 1) bzw „barcoding“-Gens. Zum ersten Mal für die südchilenische Fjordregion wurde mit dem Ansatz der integrativen Taxonomie die dortige Dekapoda-Fauna erfasst und analysiert. Nahe verwandte Arten der Gattungen Eurypodius Guérin, 1825 und Acanthocyclus Lucas, in H. Milne Edwards & Lucas, 1844, die morphologisch schwer zu trennen sind, konnten neu charakterisiert werden. In der Arbeit wurden klassische, morphologische Merkmale mit molekularen, morphologieunabhängigen Merkmalen kombiniert. Durch eine vorherige Inventarisierung der südchilenischen Dekapodenfauna während zahlreicher Expeditionen in die Region konnte zudem die Basis für die taxonomische Arbeit (ca. 650 Samples sind in der Zoologischen Staatssammlung München hinterlegt) geschaffen werden. Eine ausführlichen Dokumentation mit verschiedenen bildgebenden Methoden wie der Verwendung von tiefenscharfen Aufnahmen und in situ Fotos der verschiedenen Arten dieser noch nahezu unerforschten Region bildet das Rückgrat der taxonomischen Arbeiten und ist als Kapitel in dem zweisprachigen (Spanisch und Englisch) Standardwerk für die Region publiziert (PublikationVI). / Decapod crustaceans are a highly diverse and well adapted group belonging to the phylum Arthropoda. Representatives can be found in most aquatic ecosystems and in terrestrial habitats. The huge number of species, about 17,635 recent and fossil species are known (De Grave et al., 2009), but also the old age of the group makes a systematic classification of single species difficult. Fossil decapods were dated back to the Devonian (about 415 Mya to 359,2 Mya) (Schram et al., 1978). Because of the old age of the group there has been ample time for evolution. The results of this ongoing process are reflected in an enormous morphological variety among the species. For a coherent classification of this group and species determination it could be essential to establish new morphological features and combine new methods. Furthermore a proper identification and classification of species forms the basis of various databanks and projects e.g. GenBank, Barcoding of Life (BOLD), German Barcode of Life (GBOL) and the Barcoding Fauna Bavarica show the high significance of taxonomist’s work. The aim of this dissertation is to find and establish new features for the classification of decapods by various modern morphological methods i.e. scanning electron microscopy (SEM), fluorescence microscopy and morphology independent features like the analyses of gene sequences (cytochrome oxidase subunit 1). But additionally, classical methods like the use of morphological features in a combined, integrative approach are used for species delineation. In different publications we used SEM techniques which allow us in comparison to light microscopy a closer examination of morphological features (article I, II and III). It was possible to describe the dorsal organ and the different types of setae of zoea larvae in detail and use these features for systematic classification. Furthermore we used fluorescence microscopy and DAPI staining to describe and characterize nucleus patterns in various representatives of Decapoda of the Infraorders Caridea, Anomura and Brachyura. Results of these examinations show that nucleus patterns are characteristic for each Infraorder. In Article VI this feature is discussed as possible taxonomic criterion. In recent times molecular taxonomy gains more and more in importance. Integrative taxonomy combines sequence analyses of the COI gene (cytochrome oxidase subunit 1) or “barcoding gene” with classic morphological features. It is used to characterize and analyze the decapod fauna of the southern Chilean fjord region (article V). Furthermore, on the basis of our data, it was possible to give exact species descriptions for closely related and not always clear to distinguish representatives of the genera Eurypodius Guérin, 1825 and Acanthocyclus Lucas, in H. Milne Edwards & Lucas, 1844. As a backbone for this study serve the results of an intensive inventory of the southern Chilean fiord region. During various expeditions in that region about 650 samples of decapods were collected and are now deposited for further investigations at the Bavarian State Collection of Zoology. Samples are documented in detail using different imaging methods i.e. in situ pictures and high resolution photos of the different species of this unique and unexplored region are published as a chapter in the bilingual (Spanish and English) standard work for the Chilean fjord region (article VI).

No description available.

The use of selectively bred mouse models of enhanced fear and/or anxiety-related behavior provides a unique opportunity to identify genetic targets that contribute to pathological anxiety. However, dealing with animal models needs accurate information about their phenotypes. Accordingly, high (HAB), normal (NAB) and low (LAB) anxiety-related behavior mice – a validated model of anxiety disorders - were repeatedly tested in a variety of behavioral paradigms. Whereas most tests to assess anxiety traits are based on fear of novel and open spaces, we took advantage of the inborn fear and associated avoidance of the predator odor (trimethylthiazoline (TMT)) as a measure of anxiety-related behavior. We were able to show that avoidance of TMT reflects the high anxiety phenotype of HAB mice, indicated by the decreased time animals spent in the chamber with TMT compared to NAB and LAB mice. Importantly, this result is not confounded by any deficit of the olfactory system, since mice responded to both the pleasant odor of female urine and the repugnant odor of butyric acid. To take the influence of environmental stimuli on inborn anxiety further, we next studied the impact of environmental manipulations on the genetically driven phenotype of LAB mice. Therefore, animals were exposed to a series of chronic unpredictable mild stressors (CMS). CMS-treated mice displayed increased anxiety in the TMT-avoidance test, elevated plus-maze (EPM) and light-dark box (LDB). Moreover, these animals were characterized by increased depression-like behavior and a blunted neuroendocrine regulation. Furthermore, TMT-exposure promoted a higher activation of immediate early gene expression, e.g. c-fos, in the amygdala, especially in the basolateral nuclei (BLA). c-Fos expression pattern correlated with anxiety-related behavior after CMS. Importantly, our electrophysiological studies also indicated a higher activation of amygdala in LAB mice after CMS treatment. Since corticotropin releasing hormone (CRH) is one of the most important mediators of amygdala activity and is largely involved in the regulation of the anxiety-related behavior, we hypothesized that environmental influences are translated via an altered CRH system. Previous experiments had shown that enriched environment (EE) induced a down-regulation of Crhr1. Here, we report that CMS induced higher expression of Crhr1 in the BLA of LAB mice, in contrast to EE. Thus, these data indicate, that Crhr1 expression might be plastic in response to both, beneficial and detrimental, environmental factors. Thereafter, we studied the role of DNA methylation as a probable mechanism behind the different gene expression. Using pyrosequencing of the bisulfite-converted DNA, one specific CpG site (CpG1) of Crhr1 was found to be higher methylated after both treatments. In order to evaluate functional importance of this modification, we tested the impact of CpG1 methylation on promoter activity using the luciferase assay and observed that the presence of methylation reduced promoter activity. Moreover, elevated methylation decreased the binding efficiency of the transcription factor Yin Yang 1 (YY1) as indicated by electrophoretic mobility shift assay (EMSA). Furthermore, we analyzed whether a higher expression of YY1 in the BLA of LAB mice, observed after CMS, contributed to the elevation of Crhr1. Indeed, overexpression of YY1 in the neuronal cell culture enhanced both Crhr1 expression and Crhr1 promoter activity. Finally, we estimated the effects of combininig CpG1 site-specific methylation with YY1 overexpression on Crhr1 promoter activity and tested whether in vitro overexpression of YY1 induced methylation of CpG1. Altogether, our data suggest that even a rigid genetic predisposition to low anxiety-related behavior could be rescued by environmental modification and provide evidence that the epigenetic regulation of Crhr1 expression in the BLA is a possible underlying mechanism behind.

Le réflexe naturel d’une cellule eucaryote, soumise à un stress (ex : radiations, drogues anti-cancers…), est d’activer des mécanismes de défense afin de s’adapter aux conditions extrêmes imposées, leur permettant de survivre. Un des mécanismes activé en condition de stress est l’inhibition de l’initiation de la traduction menant à la formation de granules de stress (GS). Les GS sont des corps cytoplasmiques dynamiques renfermant des facteurs d’initiation de la traduction, des ARNms, des protéines de liaison à l’ARN ainsi que des molécules de signalisation impliquées dans les voies de mort cellulaire. La formation des GS fut identifiée comme un évènement clé inactivant les voies de mort cellulaire, constituant donc un mécanisme majeur de survie, qui dans le cas du cancer peut engendrer une chimiorésistance. Nous avons précédemment conduit un criblage des facteurs d’initiations de la traduction impliqués dans la formation des GS. Ces travaux (Mazroui et al, 2006 ; Mokas et al, 2009) ont permis d’identifier plusieurs facteurs dont l’inactivation induit la formation des GS. Par contre, l’inactivation du facteur eIF4E, qui est responsable de la reconnaissance des ARNms lors de l’initiation de la traduction, n’induit pas la formation des GS. Mon travail de thèse a permis de mettre en évidence un nouveau rôle du facteur d’initiation de la traduction eIF4E ainsi que son partenaire eIF4GI dans la formation des GS induites par le traitement chimiothérapeutique Bortezomib. Ce rôle est stimulé par la voie oncogénique mTORC1, qui est la voie de signalisation responsable de l’interaction eIF4E-eIF4GI. De plus, notre étude a démontré que l’inhibition spécifique d’eIF4E, d’eIF4GI ou l’inactivation de mTORC1 empêche l’activation des voies anti-apoptotiques associées au GS, sensibilisant ainsi les cellules cancéreuses aux traitements chimiothérapeutiques. Néanmoins, la formation des GS n’est pas restreinte au Bortezomib. En effet, notre criblage des drogues chimiothérapeutiques a identifié le Sorafenib (Nevaxar®) et le Lapatinib (Tykerb/Tyverb®) comme deux puissants inducteurs des GS au sein des cellules cancéreuses. En conclusion, ces travaux ont mis en lumière un nouveau mécanisme de formation des GS ainsi que deux potentiels inducteurs d’assemblage de ces granules. / The natural reflex of a eukaryotic cell under stress (e.g.: radiation, anti-cancer drugs, thermal or oxidative stress) is to activate defense mechanisms to adapt to extreme conditions imposed, allowing them to survive. One mechanism activated under stress conditions is the inhibition of translation initiation leading to the formation of stress granules (SG). SG are dynamic cytoplasmic body containing translation initiation factors, mRNAs, RNA binding proteins and signaling molecules involved in cell death pathways. SG formation was identified as a key event inactivating cell death pathways, thus establishing a major survival mechanism, which in the case of cancer can lead to drug resistance. We previously conducted a screening of the translation initiation factors involved in the SG formation. These works (Mazroui et al, 2006; Mochas et al, 2009) have identified several factors that inactivation induces the formation of GS. For cons, the inactivation of factor eIF4E, which is responsible for the recognition of mRNAs during translation initiation, does not induce the formation of SG. My thesis has highlighted a new role for the translation initiation factors eIF4E and its partner eIF4GI in the SG formation induced by chemotherapeutic drug Bortezomib. This role is stimulated by oncogenic mTORC1 pathway, which is the key regulator of the eIF4E-eIF4GI interaction. In addition, our study demonstrated that specific inhibition of eIF4E, eIF4GI or the inactivation of mTORC1 prevents anti-apoptotic pathways associated with SG and sensitizing cancer cells to chemotherapeutic treatments. The SG formation is not restricted to Bortezomib. Indeed, our screening of chemotherapeutic drugs has identified Sorafenib (Nevaxar ®) and Lapatinib (Tykerb / Tyverb ®) as two potent inducers of SG in cancer cells. Our results indicate that the mechanism of action of these two drugs appears to be similar to Bortezomib and they induce the formation of SG by inhibiting translation initiation. In addition, the formation of SG induced by Sorafenib or Lapatinib also seems to depend on the eIF4E-eIF4GI complex formation. Therefore, my work provides a general role of eIF4E-eIF4GI interaction in the assembly of SG and the cancer cells resistance to chemotherapy.

Les cassures double-brin de l'ADN, lorsque incorrectement réparées, peuvent avoir des conséquences fatales telles que des délétions et des réarrangements chromosomiques, favorisant la carcinogenèse. La poly(ADP-ribosyl)ation réalisée par la protéine poly(ADP-ribose) polymérase-1 (PARP-1) est l'une des premières modifications post-traductionnelles qui se produisent en réponse aux dommages à l'ADN. La PARP-1 utilise la nicotinamide pour générer un polymère chargé négativement, nommé poly(ADP-ribose) polymère (PAR), lequel est attaché en majorité à la PARP-1 elle-même ainsi qu'à d'autres protéines cibles. Le PAR a récemment été reconnu comme un signal de recrutement pour certaines protéines de réparation aux sites de dommages à l'ADN, mais un débat est en cours quant au rôle précis de la PARP-1 et du PAR dans la réponse aux dommages de l'ADN. Au cours de mon projet de doctorat, nous avons pu confirmer que les protéines qui se retrouvent en complexe avec le PAR immédiatement après les dommages à l'ADN sont principalement des facteurs de réparation. Étonnamment, les complexes protéiques associés au PAR pendant la période de récupération suite aux dommages sont enrichis en facteurs de liaison à l'ARN. Toutefois, la protéine liant l'ARN la plus abondante que nous avons détectée dans l'interactome du PAR, soit NONO, ne suit pas cette dernière cinétique puisqu'elle est fortement enrichie immédiatement après les dommages à l'ADN. Notre étude subséquente de NONO dans la réponse aux cassures double-brin de l'ADN a étonnamment révélé une implication directe de celle-ci par le mécanismede réparation de jonction des extrémités non-homologues. En plus, nous avons constaté que NONO se lie fortement et spécifiquement au PAR via son motif 1 de la reconnaissance de l'ARN, soulignant la compétition entre les PAR et l'ARN pour le même site de liaison. Fait intéressant, le recrutement in vivo de NONO aux sites de dommages de l'ADN dépend entièrement du PAR et nécessite le motif 1 de la reconnaissance de l'ARN. En conclusion, nos résultats établissent NONO comme une nouvelle protéine impliquée dans la réponse aux cassures double-brin de l'ADN et plus généralement démontrent un autre niveau de complexité supplémentaire dans l'interdépendance de la biologie de l'ARN et la réparation de l'ADN. / DNA double-strand breaks are potentially lethal lesions, which if not repaired correctly, can have harmful consequences such as carcinogenesis promoted by chromosome deletions and rearrangements. Poly(ADP-ribosyl)ation carried out by poly(ADP-ribose) polymerase 1 (PARP-1) is one of the first posttranslational modifications occurring in response to DNA damage. In brief, PARP-1 uses nicotinamide to generate a negatively charged polymer called poly(ADP-ribose) polymer (PAR), that can be attached to acceptor proteins, which is to a large extent PARP-1 itself. PAR has recently been recognized as a recruitment signal for key DNA repair proteins to sites of DNA damage but the precise role of PARP-1 and its catalytic product PAR in the DNA damage response are still a matter of ongoing debate. Throughout my doctoral work, we confirmed that the proteins in complex with PAR promptly after DNA damage are mostly DNA repair proteins, whereas during the period of recovery from DNA damage, the PAR interactome is highly enriched with RNA processing factors. Interestingly, one of the most abundant RNA-binding proteins detected in the PAR interactome, namely NONO, did not follow these kinetics as it was highly enriched immediately after DNA damage in the DNA repair protein complexes centered on PAR. Our subsequent investigation of NONO in the DNA damage response to double-strand breaks strikingly revealed a direct implication for NONO in repair by nonhomologous end joining (NHEJ). Moreover, we found that NONO strongly and specifically binds to PAR through its RNA-recognition motif 1 (RRM1), highlighting competition between PAR and RNA for the same binding site. Remarkably, the in vivo recruitment of NONO to DNA damage sites completely depends on PAR and requires the RRM1 motif. In conclusion, our results establish NONO as a new protein implicated in the DNA damage response to double-strand break and in broader terms add another layer of complexity to the cross-talk between RNA-biology and DNA repair.