Tables show recombination frequencies +/ SEM of n independent crosses, with numbers in parentheses showing the percentages relative to controls (pJK148 emptyintegrants). protein localization and stability, with several CDK sites and regulatory sequences being conserved. Keywords:CDK, Meiosis, Rad51, Recombination, Swi5-Sfr1 Subject terms:Cell LOXO-101 (ARRY-470, Larotrectinib) Cycle; DNA Replication, Recombination & Repair == Synopsis == Accessory factors of Rad51 recombinase are entry points for intricate regulation of meiotic recombination. Here, fission yeast CDK is found to ensure proper chromosome distribution and faithful genome transmission into meiotic products by Swi5-Sfr1 restriction in late meiotic prophase. Sfr1 is heavily phosphorylated by CDK at the end of meiotic prophase. Sfr1 phosphorylation impairs Rad51 recombinase binding and its stable chromosome loading. Sfr1 phosphorylation contributes to dismantling Rad51-mediated homolog invasions prior to chromosome segregation. Unphosphorylated Sfr1 increases cellular propensities for retaining Rad51 and missegregating chromosomes. Swi5-Sfr1 restriction ensures homolog invasions are dismantled in a timely manner to guarantee proper chromosome distribution and faithful genome transmission into the meiotic products. == Introduction == Meiosis is the developmental program that ensures the genome transmission from one generation to the next in sexually reproducing organisms. In sharp contrast to mitotic dividing cells, meiosis is linked to the generation of genetic variability which is the driving force of evolution. This is achieved by the assortment of the parental chromosomes in the meiotic products (gametes), as well as by recombination between them (physical exchange of genetic material between each pair of homologous chromosomes). Recombination is remarkably important, since it also imposes a stable architecture on the pair of homologs that ensures their correct orientation and faithful segregation to opposite poles of the cell during the first meiotic division (reductional chromosome segregation) (Marston and Amon,2004; Petronczki et al,2003). Chromosomes without reciprocal or with misplaced exchanges missegregate and produce gametes with an abnormal number of chromosomes. This underlies the high frequency of spontaneous miscarriages in human conceptions as well as the severe congenital defects associated to genetic syndromes (Hassold and Hunt,2021). As a key feature of meiosis, recombination is a LOXO-101 (ARRY-470, Larotrectinib) complex process under a very tight regulation (Hunter,2015; Keeney et CXCR7 al,2014; Phadnis et al,2011; Yadav and Claeys Bouuaert,2021). Meiotic recombination is the outcome of the repair of programmedDouble-StrandBreaks (DSBs), which are introduced in the DNA at early meiosis (prophase) by the conserved meiosis-specific Spo11 transesterase and its accessory proteins (Arter and Keeney,2023; Bergerat et al,1997; Hunter,2015; Keeney et al,1997; Yadav and Claeys Bouuaert,2021). After Spo11 removal from break sites, single-stranded DNA (ssDNA) nucleofilaments are generated by endonucleolytic resection of the break ends. Coated with the strand exchange proteins Rad51 and Dmc1, these nucleofilaments invade the homologous chromosome searching for a repair template (Brown and Bishop,2014). The fate of this invasion is an important point of regulation. If the invasion is stabilized, intermediates mature into interhomolog joint molecules (IH JM; Holliday junctions) that when resolved by structure-selective endonucleases (SSE) can generatecrossovers (COs, reciprocal exchange between the pair of homologs). The physical links provided by COs ensure the reductional chromosome segretation at the first meiotic division. On the other hand, the counteraction of helicases dissolves the invasion, which facilitates the reannealing with the sister chromatid in the original chromosome (Synthesis-Dependent Strand Annealing pathway, SDSA) and produces nonreciprocal exchanges between the parental chromosomes (non-crossovers, NCOs) (Hunter,2015; Lorenz,2017; Lorenz et al,2014; Lorenz et al,2012). In addition, template choice is also important for the recombination outcome; invasion can be established with the homologous chromosome (interhomolog, IH) or with the sister chromatid (intersister, IS), and the preferential template choice varies locally and between species (Hyppa and Smith,2010). The loading LOXO-101 (ARRY-470, Larotrectinib) to ssDNA and the activity of Rad51 and Dmc1 recombinases require a number of conserved accessory proteins (Brown and Bishop,2014; Tsubouchi et al,2021). In fission yeast, it has been proposed that Rad51/Dmc1 accessory-complexes Swi5Sfr1, Rad55Rad57, and Rlp1-Rdl1-Sws1 protect invasion intermediates from the unwinding action of FANCM-type Fml1 and RecQ-type Rqh1 helicases, promoting Holliday junctions.