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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
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Publication Open Access Crosstalk between autophagy and DNA repair systems(TÜBİTAK, 2021) Demirbağ Sarıkaya, Sinem; Çakır, Hatice; Gözüaçık, Devrim; Akkoç, Yunus; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 40248; N/AAutophagy and DNA repair are two essential biological mechanisms that maintain cellular homeostasis. Impairment of these mechanisms was associated with several pathologies such as premature aging, neurodegenerative diseases, and cancer. Intrinsic or extrinsic stress stimuli (e.g., reactive oxygen species or ionizing radiation) cause DNA damage. As a biological stress response, autophagy is activated following insults that threaten DNA integrity. Hence, in collaboration with DNA damage repair and response mechanisms, autophagy contributes to the maintenance of genomic stability and integrity. Yet, connections and interactions between these two systems are not fully understood. In this review article, current status of the associations and crosstalk between autophagy and DNA repair systems is documented and discussed.Publication Open Access In silico drug repositioning against human NRP1 to block SARS-CoV-2 host entry(TÜBİTAK, 2021) Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Gül, Şeref; Researcher; Graduate School of Sciences and EngineeringDespite COVID-19 turned into a pandemic, no approved drug for the treatment or globally available vaccine is out yet. In such a global emergency, drug repurposing approach that bypasses a costly and long-time demanding drug discovery process is an effective way in search of finding drugs for the COVID-19 treatment. Recent studies showed that SARS-CoV-2 uses neuropilin-1 (NRP1) for host entry. Here we took advantage of structural information of the NRP1 in complex with C-terminal of spike (S) protein of SARSCoV-2 to identify drugs that may inhibit NRP1 and S protein interaction. U.S. Food and Drug Administration (FDA) approved drugs were screened using docking simulations. Among top drugs, well-tolerated drugs were selected for further analysis. Molecular dynamics (MD) simulations of drugs-NRP1 complexes were run for 100 ns to assess the persistency of binding. MM/GBSA calculations from MD simulations showed that eltrombopag, glimepiride, sitagliptin, dutasteride, and ergotamine stably and strongly bind to NRP1. In silico Alanine scanning analysis revealed that Tyr(297), Trp(301), and Tyr(353) amino acids of NRP1 are critical for drug binding. Validating the effect of drugs analyzed in this paper by experimental studies and clinical trials will expedite the drug discovery process for COVID-19.Publication Open Access Song overlapping, noise, and territorial aggression in great tits(Oxford University Press (OUP), 2020) Avşar, Alican; Bilgin, C. Can; Department of Psychology; Department of Psychology; Akçay, Çağlar; Porsuk, Yasin Kağan; Çabuk, Dilan; Faculty Member; Teaching Faculty; College of Social Sciences and Humanities; Graduate School of Social Sciences and Humanities; 272053; N/A; N/ACommunication often happens in noisy environments where interference from the ambient noise and other signalers may reduce the effectiveness of signals which may lead to more conflict between interacting individuals. Signalers may also evolve behaviors to interfere with signals of opponents, for example, by temporally overlapping them with their own, such as the song overlapping behavior that is seen in some songbirds during aggressive interactions. Song overlapping has been proposed to be a signal of aggressive intent, but few studies directly examined the association between song overlapping and aggressive behaviors of the sender. In the present paper, we examined whether song overlapping and ambient noise are associated positively with aggressive behaviors. We carried out simulated territorial intrusions in a population of great tits (Pares major) living in an urban-rural gradient to assess signaling and aggressive behaviors. Song overlapping was associated negatively with aggressive behaviors males displayed against a simulated intruder. This result is inconsistent with the hypothesis that song overlapping is an aggressive signal in this species. Ambient noise levels were associated positively with aggressive behaviors but did not correlate with song rate, song duration, or song overlapping. Great tits in noisy urban habitats may display higher levels of aggressive behaviors due to either interference of noise in aggressive communication or another indirect effect of noise.Publication Open Access Proximity mapping of the microtubule plus-end tracking protein SLAIN2 using the BioID approach(TÜBİTAK, 2020) Department of Molecular Biology and Genetics; Department of Molecular Biology and Genetics; Karalar, Elif Nur Fırat; Faculty Member; College of Sciences; 206349The centrosome is the main microtubule-organizing center of animal cells, which plays key roles in critical cellular processes ranging from cell division to cellular signaling. Accordingly, defects in the structure and function of centrosomes cause various human diseases such as cancer and primary microcephaly. To elucidate the molecular defects underlying these diseases, the biogenesis and functions of the centrosomes have to be fully understood. An essential step towards addressing these questions is the identification and functional dissection of the full repertoire of centrosome proteins. Here, we used high-resolution imaging and showed that the microtubule plus-end tracking protein SLAIN2 localizes to the pericentriolar material at the proximal end of centrioles. To gain insight into its cellular functions and mechanisms, we applied in vivo proximity-dependent biotin identification to SLAIN2 and generated its proximity interaction map. Gene ontology analysis of the SLAIN2 interactome revealed extensive interactions with centriole duplication, ciliogenesis, and microtubule-associated proteins, including previously characterized and uncharacterized interactions. Collectively, our results define SLAIN2 as a component of pericentriolar material and provide an important resource for future studies aimed at elucidating SLAIN2 functions at the centrosome.