Pch2 Is A Hexameric Ring Atpase That Remodels The Meiotic Chromosome Axis Protein Hop1
Bibliographic record
Abstract
In most organisms, the accurate segregation of chromosomes during the first meiotic division requires at least one crossover between each pair of homologous chromosomes. Crossovers form in meiosis from programmed double-strand breaks (DSBs) that are preferentially repaired using the homologous chromosome as a template. The PCH2 gene of budding yeast is required to establish proper meiotic chromosome structure, and to regulate meiotic DSB repair outcomes. PCH2 was also found to promote meiotic checkpoint functions, and to maintain ribosomal DNA stability during meiosis. The major focus of my thesis research has been to elucidate the molecular mechanism of Pch2 function. Pch2 contains an AAA (ATPases Associated with diverse cellular Activities) domain and is conserved in worms, fruit flies, and mammals. I performed the first detailed biochemical analysis of Pch2, and found that purified Pch2 oligomerizes into single hexameric rings in the presence of nucleotide. In addition, I showed that Pch2 directly binds to Hop1, a critical component of the synaptonemal complex that facilitates DSB repair to form crossovers. Interestingly, Hop1 binding by Pch2 induces large conformational changes in Pch2 hexamers, suggesting that Pch2 hexamers exert mechanical forces on Hop1. Importantly, I demonstrate that Pch2 subunits coordinate their ATP hydrolysis activities to displace Hop1 from large DNA substrates, providing an explanation for the altered localization of Hop1 in pch2[DELTA] mutants that was previously observed. Based on these results and other genetic and cell biological evidences I propose that Pch2 impacts multiple meiotic chromosome functions by directly regulating Hop1 localization. The second part of my thesis involves analyzing the pro-crossover Msh4-Msh5 complex, which facilitates interhomolog crossover formation by stabilizing recombination intermediates. To analyze Msh4-Msh5 function, I assayed spore viability and crossover levels for 57 msh4 and msh5 mutants and identified threshold mutants that showed wild-type spore viability but significantly decreased crossover levels. These findings suggest that a buffering mechanism exists to ensure the obligate crossover when overall crossover levels are reduced.
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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".