Mechanisms in Early Meiosis
Sexual Reproduction and Meiosis
Meiosis follows a defined sequence of events, starting with DNA synthesis (S-phase), where chromosomes are replicated to form identical sister chromatids, linked by cohesin rings. During meiosis, however, it is necessary to link homologous chromosomes (homologs). The cell makes programmed double strand breaks in its own genome, which are then repaired via homologous recombination. In meiosis, the repair of these DNA breaks is directed to the homologs. Some breaks are repaired as crossovers which link the homologs together. Once linked, the homologous chromosomes are separated (end of meiosis I), and the sisters are subsequently separated (meiosis II).
How is double strand break formation controlled?
The Meiotic Axis
Meiotic chromosomes form a distinct loop-axis architecture, with loops of chromatin emanating from a proteinaceous axis. The double-stranded DNA breaks (DSBs) that initiate meiotic recombination are made in the loops, yet the DSB-forming machinery associates with the axis. We reconstitute axial protein complexes and explore how they associate with chromatin and with DSB-forming accessory proteins (for example in Rousová et al., eLife, 2021). We are gaining important insights into how the DSB machinery associates with the axis, and how the status of the axis regulates both DSB formation and subsequent crossover formation.
How are crossovers regulated to ensure all homologs are linked?
Pro-crossover Factors
Crossovers, essential for the linkage of homologous chromosomes, are not formed randomly in most organisms. A group of proteins collectively referred to as "ZMM" both promote crossover formation and regulate their distribution along the length of the chromosomes. We explore how ZMM proteins associate with one another, and examine their nucleic acid dependent activities in vitro. Some of the ZMM proteins recognise early recombination intermediates (left) and protect them from being disassembled(see Altmannova et al., Nucleic Acids Research, 2023).
Meiosis generates diversity, but how much diversity is there in meiosis?
Meiosis across evolution
Although meiosis is ubiquitous and well conserved throughout evolution, there are some notable variations. Also, meiosis is poorly studied outside of conventional model organisms. We are interested in the diversity of meiosis, exploring the crossover free meiosis in male fruit flies (Kabakci et al., PLoS Genetics 2022), and more recently, the formation of the meiotic axis in the brown alga Ectocarpus (Kane et al., 2025). Through these fundamental approaches we will gain insights into which mechanisms of meiosis are truly conserved, and how we might exploit the divergences that exist in other species.
