Novel Insights into Nuclear Localization of Proteins Crucial for Chromatin Assembly Metabolism in Saccharomyces cerevisiae
Notice bibliographique
Résumé
Proper chromatin assembly is critical for maintaining genetic integrity, accurate DNA repair as well as gene expression. These processes are fundamental in eukaryotic cells, and studying them in the powerful budding yeast genetic model allows us to uncover novel mechanisms in the regulation of chromatin assembly and dynamics. Chromatin is assembled by replication-independent or replication-coupled pathways, where histone chaperones (HCs) and modifying enzymes (such as HATs) are key factors in regulating these mechanisms. Alterations in these factors have been implicated in cancer and multiple human diseases. Therefore, the goal is to investigate the involvement of histone chaperones and HATs in the regulation of chromatin assembly. One interesting aspect of my research is the evolutionarily conserved histone H3-H4-specific chaperone Hif1. Hif1, as well as its human homolog NASP, is involved in a wide array of chromatin-related processes, including histone H3-H4 transport, chromatin assembly and DNA repair. This research elucidated several functional aspects of Hif1. I revealed that an acidic region interpreting the second TPR domain of Hif1 is essential for Hif1 physical interactions with Hat2 (HAT-B complex), H4 (Histone H3-H4), as well as Asf1. Moreover, this study was the first to demonstrate that the nuclear localization of Hif1 is regulated by a classical nuclear localization sequence (cNLS) located at its C-terminus. Another aspect of my research is to investigate the role of putative cNLSs in the complex interplay between Rtt109, Vps75 and Asf1 in H3K56ac in S cerevisiae. In yeast, H3K56ac plays a key role in DNA replication and genome stability. Therefore, I began to investigate the fungus- specific HAT Rtt109 that is required for the Asf1-dependant acetylation of K56 on histone H3. Here, I showed that the putative cNLS of Rtt109 is indeed a functional cNLS. I further provided evidence that Rtt109 is imported to the nucleus through its cNLS in a redundant manner with Vps75. Furthermore, I identified a cNLS within the acidic C-terminus of Asf1 in S. cerevisiae, which has a critical role in Asf1 nuclear localization. My work demonstrates that this cNLS of Asf1 is also required for full H3K56 acetylation. Additionally, this research expounds on how the cNLSs of Hif1, Rtt109 and Asf1 can mediate their nuclear import pathway. I specifically showed that Kap123 is partially involved in Rtt109 nuclear localization and import, conversely, Hif1 and Asf1 might use Kap123 as a secondary transporter. Finally, I provide evidence that Kap95 might be one major importin that plays an important role in Hif1, Asf1 and Rtt109 nuclear import pathway. To my knowledge, this study is the first to reveal the presence of functional cNLS motifs within Hif1, Asf1 and Rtt109. This novel finding may provide insights into learning about analogous pathways in human cells.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».