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Dual Histone Methyl Reader ZCWPW1 Facilitates Repair of Meiotic Double Strand Breaks

View ORCID ProfileMohamed Mahgoub, Jacob Paiano, Melania Bruno, Wei Wu, Sarath Pathuri, Xing Zhang, Sherry Ralls, Xiaodong Cheng, Andre Nussenzweig, Todd Macfarlan
doi: https://doi.org/10.1101/821603
Mohamed Mahgoub
The Eunice Kennedy Shriver National Institutes of Child Health and Human Development, NIH, Bethesda, MD, USA
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  • ORCID record for Mohamed Mahgoub
Jacob Paiano
Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USAImmunology Graduate Group, University of Pennsylvania, Philadelphia, PA, USA
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Melania Bruno
The Eunice Kennedy Shriver National Institutes of Child Health and Human Development, NIH, Bethesda, MD, USA
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Wei Wu
Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA
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Sarath Pathuri
Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Xing Zhang
Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Sherry Ralls
The Eunice Kennedy Shriver National Institutes of Child Health and Human Development, NIH, Bethesda, MD, USA
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Xiaodong Cheng
Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Andre Nussenzweig
Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA
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Todd Macfarlan
The Eunice Kennedy Shriver National Institutes of Child Health and Human Development, NIH, Bethesda, MD, USA
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  • For correspondence: todd.macfarlan@nih.gov
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Summary

Meiotic crossovers result from homology-directed repair of double strand breaks (DSBs). Unlike yeast and plants, where DSBs are generated near gene promoters, in many vertebrates, DSBs are enriched at hotspots determined by the DNA binding activity of the rapidly evolving zinc finger array of PRDM9 (PR domain zinc finger protein 9). PRDM9 subsequently catalyzes tri-methylation of lysine 4 and lysine 36 of Histone H3 in nearby nucleosomes. Here, we identify the dual histone methylation reader ZCWPW1, which is tightly co-expressed during spermatogenesis with Prdm9 and co-evolved with Prdm9 in vertebrates, as an essential meiotic recombination factor required for efficient synapsis and repair of PRDM9-dependent DSBs. In sum, our results indicate that the evolution of a dual histone methylation writer/reader system in vertebrates facilitated a shift in genetic recombination away from a static pattern near genes towards a flexible pattern controlled by the rapidly evolving DNA binding activity of PRDM9.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
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Posted October 29, 2019.
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Dual Histone Methyl Reader ZCWPW1 Facilitates Repair of Meiotic Double Strand Breaks
Mohamed Mahgoub, Jacob Paiano, Melania Bruno, Wei Wu, Sarath Pathuri, Xing Zhang, Sherry Ralls, Xiaodong Cheng, Andre Nussenzweig, Todd Macfarlan
bioRxiv 821603; doi: https://doi.org/10.1101/821603
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Dual Histone Methyl Reader ZCWPW1 Facilitates Repair of Meiotic Double Strand Breaks
Mohamed Mahgoub, Jacob Paiano, Melania Bruno, Wei Wu, Sarath Pathuri, Xing Zhang, Sherry Ralls, Xiaodong Cheng, Andre Nussenzweig, Todd Macfarlan
bioRxiv 821603; doi: https://doi.org/10.1101/821603

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