Distinct and interdependent functions of three RING proteins regulate recombination during mammalian meiosis

• 成果类型: Article
• 署名作者: Ito, Masaru; Yun, Yan; Kulkarni, Dhananjaya S.; Lee, Sunkyung; Sandhu, Sumit; Nunez, Briana; Hu, Linya; Lee, Kevin; Lim, Nelly; Hirota, Rachel M.; Prendergast, Rowan; Huang, Cynthia; Huang, Ivy; Hunter, Neil
• 署名单位: Howard Hughes Medical Institute; University of California System; University of California Davis; University of California System; University of California Davis; University of Osaka; Brown University; University of California System; University of California Davis
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13867
• DOI: 10.1073/pnas.2412961121
• 发表日期: 2025-01-14
• 关键词: crossover maturation; synaptonemal complex; ubiquitin ligase; wild population; aneuploidy; rnf212; roles; interference; molecule; FAILURE

摘要

During meiosis, each pair of homologous chromosomes becomes connected by at least one crossover, as required for accurate segregation, and adjacent crossovers are widely separated thereby limiting total numbers. In coarsening models, this crossover patterning results from nascent recombination sites competing to accrue a limiting pro- crossover RING- domain protein (COR) that diffuses between synapsed chromosomes. Here, we delineate the localization dynamics of three mammalian CORs in the mouse and determine their interdependencies. RNF212, HEI10, and the newest member RNF212B show divergent spatiotemporal dynamics along synapsed chromosomes, including profound differences in spermatocytes and oocytes, that are not easily reconciled by elementary coarsening models. Contrasting mutant phenotypes and genetic requirements indicate that RNF212B, RNF212, and HEI10 play distinct but interdependent functions in regulating meiotic recombination and coordinating the events of meiotic prophase- I by integrating signals from DNA breaks, homolog synapsis, the cell- cycle, and incipient crossover sites.