{"id":414,"title":"Separable downmodulation of meiotic axis protein deposition and DNA break induction at chromosome ends","title_zh":"酵母染色体末端减数分裂轴蛋白沉积与DNA双链断裂诱导的可分离下调机制","url":"https://pubmed.ncbi.nlm.nih.gov/42885671","doi":"10.7554/elife.110189","pmid":"42885671","journal":"Elife","kind":"paper","lang":"en","published_at":"2026-10-16T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Raghavan AR","May K","Subramanian VV","Blitzblau HG","Patel NJ","Houseley J","Hochwagen A"],"primary_topic":"oocyte","topics":[{"slug":"oocyte","score":4.0,"hits":["meiotic"]},{"slug":"repro-genetics","score":1.0,"hits":["meiotic recombination"]},{"slug":"ethics-policy","score":1.0,"hits":["regulation"]}],"topic_score":4.0,"preference_score":0.0,"preference_labels":[],"llm_score":62.0,"final_score":68.0,"score_dims":{"novelty":74,"rigor":78,"impact":52,"relevance":42,"translation":32},"recommend_reason":"机制设计扎实，提出轴蛋白沉积与DSB诱导可分离调控的新认识，对理解减数分裂重组在染色体末端的抑制有基础价值；但研究对象为酵母，与临床生殖医学和ART距离较远，仅供关注减数分裂重组调控机制的研究者浏览。","keywords":["减数分裂重组","端粒","DNA双链断裂","Dot1","Sir复合物","酿酒酵母"],"selected":1,"story_id":383,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-top-journals","source_name":"PubMed · CNS/大子刊/四大医学刊（生殖相关）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"elife","journal_tier":"general-top","journal_if":6.4,"is_mock":false,"summary_zh":"该研究以酿酒酵母为模型，探讨端粒附近20 kb内重组促进性轴蛋白富集偏低和DNA双链断裂（DSB）诱导受到抑制的机制。结果显示，多种常具染色体特异性的抑制机制共同参与：轴蛋白抑制与顺式编码信号及编码密度降低相关，并依赖组蛋白甲基转移酶Dot1与Sir沉默复合物；Dot1部分不依赖其经典底物H3K79来抑制Sir活性。另外，Sir复合物（而非Dot1）通过限制启动子开放度，抑制少数隐匿热点的DSB诱导。在dot1与sir3突变体中，染色体末端DSB减少仍大部分存在，说明还有其他调控层次。","summary":"In many organisms, meiotic crossover recombination is suppressed near the extreme ends of chromosomes. Here, we show that multiple, often chromosome-specific, suppressive mechanisms with differing ranges contribute to the consistently low enrichment of recombination-promoting axis proteins and the downregulation of DNA double-strand breaks (DSBs) within 20 kb of telomeres in Saccharomyces cerevisiae. Suppression of axis proteins is associated with cis-encoded signals and correlates with reduced coding density, although whether this sequence feature actively drives suppression remains to be determined. In addition, axis protein suppression requires the histone methyltransferase Dot1 and the Sir silencing complex. We show that Dot1 suppresses Sir complex activity at least in part independently of its canonical target, H3K79, to downmodulate axis protein deposition near chromosome ends. In parallel, the Sir complex, but not Dot1, suppresses the induction of DSBs at a small number of cryptic hotspots by limiting the openness of promoters, the preferred sites of meiotic DSB formation. Much of the reduced DSB induction near chromosome ends persists in dot1 and sir3 mutants, indicating that additional layers of regulation contribute to the robust reduction of meiotic recombination effectors near chromosome ends.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}