Novel Insights into Nuclear Localization of Proteins Crucial for Chromatin Assembly Metabolism in Saccharomyces cerevisiae
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".