TY - JOUR
T1 - Novel mechanistic insights into the role of Mer2 as the keystone of meiotic DNA break formation
AU - Rousová, Dorota
AU - Nivsarkar, Vaishnavi
AU - Altmannova, Veronika
AU - Raina, Vivek B
AU - Funk, Saskia K
AU - Liedtke, David
AU - Janning, Petra
AU - Müller, Franziska
AU - Reichle, Heidi
AU - Vader, Gerben
AU - Weir, John R
N1 - © 2021, Rousová et al.
PY - 2021/12/24
Y1 - 2021/12/24
N2 - 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.
AB - 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.
KW - Chromatin/metabolism
KW - DNA Breaks, Double-Stranded
KW - Meiosis
KW - Saccharomyces cerevisiae/genetics
KW - Saccharomyces cerevisiae Proteins/genetics
U2 - 10.7554/eLife.72330
DO - 10.7554/eLife.72330
M3 - Article
C2 - 34951404
SN - 2050-084X
VL - 10
JO - eLife
JF - eLife
ER -