RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosis

April Reynolds, Huanyu Qiao, Ye Yang, Jefferson K. Chen, Neil Jackson, Kajal Biswas, J. Kim Holloway, Frédéric Baudat, Bernard De Massy, Jeremy Wang, Christer Höög, Paula E. Cohen, Neil Hunter

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Crossing-over ensures accurate chromosome segregation during meiosis, and every pair of chromosomes obtains at least one crossover, even though the majority of recombination sites yield non-crossovers. A putative regulator of crossing-over is RNF212, which is associated with variation in crossover rates in humans. We show that mouse RNF212 is essential for crossing-over, functioning to couple chromosome synapsis to the formation of crossover-specific recombination complexes. Selective localization of RNF212 to a subset of recombination sites is shown to be a key early step in the crossover designation process. RNF212 acts at these sites to stabilize meiosis-specific recombination factors, including the MutSγ complex (MSH4-MSH5). We infer that selective stabilization of key recombination proteins is a fundamental feature of meiotic crossover control. Haploinsufficiency indicates that RNF212 is a limiting factor for crossover control and raises the possibility that human alleles may alter the amount or stability of RNF212 and be risk factors for aneuploid conditions.

Original languageEnglish (US)
Pages (from-to)269-278
Number of pages10
JournalNature Genetics
Volume45
Issue number3
DOIs
StatePublished - Mar 2013

ASJC Scopus subject areas

  • Genetics

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    Reynolds, A., Qiao, H., Yang, Y., Chen, J. K., Jackson, N., Biswas, K., Holloway, J. K., Baudat, F., De Massy, B., Wang, J., Höög, C., Cohen, P. E., & Hunter, N. (2013). RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosis. Nature Genetics, 45(3), 269-278. https://doi.org/10.1038/ng.2541