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Mouse ANKRD31 Regulates Spatiotemporal Patterning of Meiotic Recombination Initiation and Ensures Recombination between X and Y Sex Chromosomes

Papanikos, Frantzeskos, Clément, Julie A.J., Testa, Erika, Ravindranathan, Ramya, Grey, Corinne, Dereli, Ihsan, Bondarieva, Anastasiia, Valerio-Cabrera, Sarai, Stanzione, Marcello, Schleiffer, Alexander, Jansa, Petr, Lustyk, Diana, Fei, Ji-Feng, Adams, Ian R., Forejt, Jiri, Barchi, Marco, de Massy, Bernard, Toth, Attila
Molecular cell 2019 v.74 no.5 pp. 1069-1085.e11
DNA damage, Y chromosome, chromosome segregation, meiosis, mice, models, proteins, spermatocytes
Orderly segregation of chromosomes during meiosis requires that crossovers form between homologous chromosomes by recombination. Programmed DNA double-strand breaks (DSBs) initiate meiotic recombination. We identify ANKRD31 as a key component of complexes of DSB-promoting proteins that assemble on meiotic chromosome axes. Genome-wide, ANKRD31 deficiency causes delayed recombination initiation. In addition, loss of ANKRD31 alters DSB distribution because of reduced selectivity for sites that normally attract DSBs. Strikingly, ANKRD31 deficiency also abolishes uniquely high rates of recombination that normally characterize pseudoautosomal regions (PARs) of X and Y chromosomes. Consequently, sex chromosomes do not form crossovers, leading to chromosome segregation failure in ANKRD31-deficient spermatocytes. These defects co-occur with a genome-wide delay in assembling DSB-promoting proteins on autosome axes and loss of a specialized PAR-axis domain that is highly enriched for DSB-promoting proteins in wild type. Thus, we propose a model for spatiotemporal patterning of recombination by ANKRD31-dependent control of axis-associated DSB-promoting proteins.