ANKRD31 regulates spatiotemporal patterning of meiotic recombination initiation and ensures recombination between heterologous sex chromosomes in mice

Papanikos, F.; Clement, J. A. J.; Testa, E.; Ravindranathan, R.; Grey, C.; Dereli, I.; Bondarieva, A.; Valerio-Cabrera, S.; Stanzione, M.; Schleiffer, A.; Jansa, P.; Lustyk, D.; Jifeng, F.; Forejt, J.; Barchi, M.; de Massy, B.; Toth, A.

doi:10.1101/423293

bioRxiv · 10.1101/423293

ANKRD31 regulates spatiotemporal patterning of meiotic recombination initiation and ensures recombination between heterologous sex chromosomes in mice

Papanikos, F.·Clement, J. A. J.·Testa, E.·Ravindranathan, R.·Grey, C.·Dereli, I.·Bondarieva, A.·Valerio-Cabrera, S.·Stanzione, M.·Schleiffer, A.·Jansa, P.·Lustyk, D.·Jifeng, F.·Forejt, J.·Barchi, M.·de Massy, B.·Toth, A.

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Abstract

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 critical component of complexes of DSB-promoting proteins which assemble on meiotic chromosome axes. Genome-wide, ANKRD31 deficiency causes delayed recombination initiation. In addition, loss of ANKRD31 alters DSB distribution owing to 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 are accompanied by a genome-wide delay in assembling DSB-promoting proteins on axes and a loss of a specialized PAR-axis domain that is highly enriched for DSB-promoting proteins. Thus, we propose a model for spatiotemporal patterning of recombination by ANKRD31-dependent control of axis-associated complexes of DSB-promoting proteins.

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Papanikos, F., Clement, J. A. J., Testa, E., Ravindranathan, R., Grey, C., Dereli, I., Bondarieva, A., Valerio-Cabrera, S., Stanzione, M., Schleiffer, A., Jansa, P., Lustyk, D., Jifeng, F., Forejt, J., Barchi, M., de Massy, B., Toth, A.. 2018-09-28. ANKRD31 regulates spatiotemporal patterning of meiotic recombination initiation and ensures recombination between heterologous sex chromosomes in mice. https://doi.org/10.1101/423293

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