Ibed [40]. Immunoprecipitated HA-Tel1 was immunodetected by Western utilizing anti-HA antibodies and is indicated with an arrow. (TIF)AcknowledgmentsWe thank S. Marcand for plasmids (pRS314-POL4, pRS314-pol4D367E) and yeast strains, T.H. Petes for the pKR5 plasmid, B. Gomez-Gonzalez and F. Cortes-Ledesma for important reading with the manuscript and D. Haun and M. Simon for style supervision. We also thank F. Cortes-Ledesma and P. Pasero for their support to finish this study.Author ContributionsConceived and created the experiments: JFR BP. Performed the experiments: JFR BP GSM. Analyzed the data: JFR BP GSM. Contributed reagents/materials/analysis tools: JFR BP AA LB. Wrote the paper: JFR BP AA LB.For many diploid organisms, the formation of haploid gametes relies on crossover (CO) recombination between homologous chromosomes for precise chromosome segregation. Recombination is initiated through meiotic prophase by the programmed induction of DNA double strand breaks (DSBs), catalyzed by the evolutionarily conserved topoisomerase-like protein Spo11 [1]. A PbTx-3 Technical Information subset of these DSBs are repaired by a specialized meiotic DSB repair pathway that makes use of the homolog as a recombination partner and generates intermediates that can be resolved as COs. This specialized repair is completed throughout the pachytene stage of meiotic prophase, in the context of meiosis-specific chromosome organization in which homologs are paired and connected along their axes by a structure generally known as the synaptonemal complex (SC). By the final stage of meiotic prophase (diakinesis), the SC hasPLOS Genetics | plosgenetics.orgdisassembled, and chromosomes have additional condensed and reorganized to reveal CO-dependent structures known as chiasmata, which connect homologous chromosomes and enable them to orient and segregate to opposite poles in the meiosis I division [2]. DSB formation should be tightly regulated to make sure productive meiosis: cells have to both turn on DSB formation to attain interhomolog COs, but additionally turn off DSB formation to enable repair and subsequent chromosome re-organization in preparation for the meiotic divisions. Thus, DSB formation and repair has to be coordinated with other elements of meiotic chromosome dynamics. Also, cells have to make enough DSBs to guarantee 1 CO per chromosome pair, but as well a lot of DSBs could cause unrepaired DNA damage and compromise genomic integrity. Whilst Spo11 catalyzes DSB formation, tiny is known about how Spo11 activity is regulated and how the timing and number of DSBs are controlled. Numerous proteins in addition to Spo11 are requiredRegulation of Meiotic DSB Formation in C. elegansAuthor SummaryFormation of haploid gametes in the course of meiosis relies on deliberate induction of DNA double-strand breaks (DSBs), followed by repair of a subset of DSBs as crossovers in between homologous chromosomes. Crossovers kind the basis of connections that enable homologs to segregate toward opposite spindle poles at meiosis I, TAK-828F custom synthesis thereby minimizing ploidy. Hence, germ cells should produce adequate DSBs to guarantee a crossover for each chromosome pair even though avoiding an excessive quantity of DSBs that may endanger their genomes. Here, we deliver insight into how this important balance is accomplished. We recognize C. elegans DSB-2 as a essential regulator of DSB formation, and we propose that its association with chromatin is an indicator of DSB competence. Disappearance of DSB-2 is a part of a coordinated transition affecting several distinct elements from the meiotic system, and.