Novel mechanistic insights into the role of Mer2 as the keystone of meiotic DNA break formation

Dorota Rousová, Vaishnavi Nivsarkar, Veronika Altmannova, Vivek B Raina, Saskia K Funk, David Liedtke, Petra Janning, Franziska Müller, Heidi Reichle, Gerben Vader, John R Weir

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review


In meiosis, DNA double-strand break (DSB) formation by Spo11 initiates recombination and enables chromosome segregation. Numerous factors are required for Spo11 activity, and couple the DSB machinery to the development of a meiosis-specific 'axis-tethered loop' chromosome organisation. Through in vitro reconstitution and budding yeast genetics, we here provide architectural insight into the DSB machinery by focussing on a foundational DSB factor, Mer2. We characterise the interaction of Mer2 with the histone reader Spp1, and show that Mer2 directly associates with nucleosomes, likely highlighting a contribution of Mer2 to tethering DSB factors to chromatin. We reveal the biochemical basis of Mer2 association with Hop1, a HORMA domain-containing chromosomal axis factor. Finally, we identify a conserved region within Mer2 crucial for DSB activity, and show that this region of Mer2 interacts with the DSB factor Mre11. In combination with previous work, we establish Mer2 as a keystone of the DSB machinery by bridging key protein complexes involved in the initiation of meiotic recombination.

Originele taal-2Engels
StatusGepubliceerd - 24 dec. 2021
Extern gepubliceerdJa


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