By Dr. Douglas R. Waverly, Professor Emeritus of Biochemistry, Yale University

Abstract. The formation of DNA double-strand breaks (DSBs) by Spo11 is tied to the loop-axis organization of meiotic chromosomes. Before DSB formation, chr

Faithful chromosome segregation during meiosis I requires tight control of interhomolog recombination. In budding yeast, the meiotic chromosome axis, built on Rec8-containing cohesin together with Red...

During meiosis the MRX complex is required for DSB formation in budding yeast. Here, the authors show the Mre11 forms DNA-dependent condensates via its C-terminal disordered tail, which further intera...

During meiosis the MRX complex is required for DSB formation in budding yeast. Here, the authors show the Mre11 forms DNA-dependent condensates via its C-terminal disordered tail, which further intera...

Long‑range chromosome encounters in cells are hard to quantify. Here, the authors induce artificial contacts in yeast and show that intra‑chromosomal interactions form faster than inter‑chromosomal on...

Meiotic prophase-I chromosomes are organized into linear arrays of chromatin loops anchored to proteinaceous axes that define the interaction interfaces for the pairing and synapsis of homologous chromosomes. Chromatin loop size and axial chromosome length are inversely correlated and vary widely both between and within species, including between the sexes. The molecular basis of this variation remains unclear. Here, we provide evidence that the small ubiquitin-like modifier, SUMO, regulates loop–axis organization in mouse meiosis. Our analysis shows that the longer axes of oocyte chromosomes contain more SUMO per unit length than the shorter axes of spermatocyte chromosomes. In mouse models, the loss of SUMO1 results in shorter axes and longer chromatin loops. Conversely, increased SUMO1 conjugation, caused by mutation of the SENP1 isopeptidase, produces longer axes with shorter loops. Axis length positively correlates with meiotic recombination. Accordingly, Sumo1 and Senp1 mutations respectively decrease and increase crossover frequency. These findings identify SUMO as a key regulator of meiotic chromosome architecture and suggest a molecular basis for the physiological variation in chromosome length and recombination rates seen among species, sexes, individuals, and individual meiocytes. ![Figure][1]</img> ### Competing Interest Statement The authors have declared no competing interest. Eunice Kennedy Shriver National Institute of Child Health and Human Development, https://ror.org/04byxyr05, R01HD109322 Guangdong Basic and Applied Basic Research Foundation, 2024A1515012907 DBT-Ramalingaswami, re-entry fellowship NIAB core grant, C0031 [1]: pending:yes

Image generated by Google Gemini I had grown weary of the constant stream and abuse of spam invitations to submit manuscripts to journals and to attend fake conferences on the other side of the wor…

The formation of DNA double-strand breaks (DSBs) by Spo11 is tied to the loop-axis organization of meiotic chromosomes. Prior to DSB formation, chromatin loops marked by histone H3K4 trimethylation be...

Holliday junctions maintain chromosome synapsis to enable crossover assurance in budding yeast.

Conditional ablation experiments show that key components of the synaptonemal complex protect double Holliday junction recombination intermediates to ensure their resolution into crossover products, which are required for accurate chromosome segregation during meiosis.

Meiotic crossover formation is critical for generating viable gametes and enhancing genetic diversity. The helicase Mer3 (HFM1 in humans) is a highly conserved factor essential for promoting crossover...

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The Mre11 nuclease, part of the conserved MRX complex involved in the repair of DNA double-strand breaks (DSBs), is also essential to initiate meiotic recombination in budding yeast by promoting Spo11-induced DSBs. Recruitment of Mre11 to meiotic DSB sites depends on Rec114-Mei4 and Mer2 (RMM) that organize the meiotic DSB machinery by a mechanism involving biomolecular condensation. Here, we explored the role of Mre11 during meiosis and its relationship to RMM condensation. We show that both Mre11 and MRX complexes form DNA-dependent, hexanediol sensitive condensates in vitro. In vivo, Mre11 assembles into DNA damage-dependent foci in vegetative cells and DSB-independent foci in meiotic cells. In vitro condensates and in vivo foci both depend on the C-terminal intrinsically-disordered region (IDR) of Mre11. Importantly, while the Mre11 IDR is dispensable for vegetative DNA repair it is essential during meiosis. The C-terminus of Mre11 forms a short alpha-helix that binds a conserved region of Mer2, and mutating residues within this interface reduces Mre11 foci and DSB formation. Finally, we identified a SUMO-interacting motif within the Mre11 IDR that enhances recruitment of Mre11 during meiosis and facilitates DSB formation. This work identifies multiple mechanisms that collaborate to recruit Mre11 during meiosis to initiate recombination. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, 802525 Fonds National de la Recherche Scientifique, Bruxelles, BE, T.0031.22 Research Council VUB, SRP95, OZR3939 National Institute of Health, US, R01GM074223

The Mre11 nuclease, part of the conserved MRX complex involved in the repair of DNA double-strand breaks (DSBs), is also essential to initiate meiotic recombination in budding yeast by promoting Spo11-induced DSBs. Recruitment of Mre11 to meiotic DSB sites depends on Rec114-Mei4 and Mer2 (RMM) that organize the meiotic DSB machinery by a mechanism involving biomolecular condensation. Here, we explored the role of Mre11 during meiosis and its relationship to RMM condensation. We show that both Mre11 and MRX complexes form DNA-dependent, hexanediol sensitive condensates in vitro. In vivo, Mre11 assembles into DNA damage-dependent foci in vegetative cells and DSB-independent foci in meiotic cells. In vitro condensates and in vivo foci both depend on the C-terminal intrinsically-disordered region (IDR) of Mre11. Importantly, while the Mre11 IDR is dispensable for vegetative DNA repair it is essential during meiosis. The C-terminus of Mre11 forms a short alpha-helix that binds a conserved region of Mer2, and mutating residues within this interface reduces Mre11 foci and DSB formation. Finally, we identified a SUMO-interacting motif within the Mre11 IDR that enhances recruitment of Mre11 during meiosis and facilitates DSB formation. This work identifies multiple mechanisms that collaborate to recruit Mre11 during meiosis to initiate recombination. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, 802525 Fonds National de la Recherche Scientifique, Bruxelles, BE, T.0031.22 Research Council VUB, SRP95, OZR3939 National Institute of Health, US, R01GM074223

Nature Cell Biology - Zhang et al. provide evidence that, during meiosis, recombination proteins assemble into active droplets, the coarsening of which partially explains the phenomenon of...

Meiotic crossovers enhance genetic diversity in sexually reproducing organisms. Here, the authors propose that the higher-order spatial organization of the meiotic chromosomes shapes sexual dimorphism...

Three recent studies report the first biochemical reconstitution of DNA double-strand break (DSB) formation by SPO11, the topoisomerase-derived transesterase that initiates meiotic recombination in sexually reproducing organisms. A central conclusion of these studies is that SPO11 is sufficient to catalyze DSBs in vitro, but cleavage is limited by the poor propensity of SPO11 to dimerize, thereby providing an effective mechanism to prevent uncontrolled breaks. The studies yield new insights into the mechanism of DNA DSB formation and raise new questions regarding the functions of SPO11 partners, the impact of the DNA substrate, the coordination between cleavage events, and the reversibility of the reaction.

A conserved feature of metazoan meiosis is that it occurs in a syncytium. Here, the authors show that intercellular bridges that connect germ cells in a syncytium are critical for ensuring proper meio...

DNA G-quadruplexes (G4s) are non–B-form DNA secondary structures that threaten genome stability by impeding DNA replication. To elucidate how G4s induce replication fork arrest, we characterized fork ...

By regulating the chromosome axis component and meiotic HORMAD, HIM-3, the conserved AAA-ATPase PCH-2 controls the number and distribution of meiotic recombination events.

A biochemical system recapitulates the hallmarks of meiotic double-strand break formation, with mouse&nbsp;SPO11 catalysing break formation in the absence of any partners and remaining covalently atta...

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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 tot...

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Transcription creates superhelical stress in DNA, challenging genome stability. Here the authors find Top2 activity is uncorrelated with transcription unless chromatin is disrupted suggesting that chr...

Homologous meiotic recombination starts with DNA double-strand breaks (DSBs) generated by SPO11 protein. SPO11 is critical for meiosis in most species but the DSBs it makes are also dangerous because ...

SPO11 initiates meiotic recombination through the induction of programmed DNA double-strand breaks (DSBs), but this catalytic activity had never been reconstituted in vitro. Here, using Mus musculus S...