Meiotic Knockdown and Complementation Reveals Essential Role of RAD51 in Mouse Spermatogenesis

Publication date: 7 February 2017
Source:Cell Reports, Volume 18, Issue 6
Author(s): Jieqiong Dai, Oleg Voloshin, Svetlana Potapova, R. Daniel Camerini-Otero
Meiotic homologous recombination (HR) is important for proper chromosomal segregation during gametogenesis and facilitates evolutionary adaptation via genomic reshuffling. In most eukaryotes, HR is mediated by two recombinases, the ubiquitous RAD51 and the meiosis-specific DMC1. The role of RAD51 in mammalian meiosis is unclear and study of its function is limited due to embryonic lethality of RAD51 knockouts. Here, we developed an in vivo meiotic knockdown and protein complementation system to study RAD51 during mouse spermatogenesis. We show that RAD51 is crucial during meiotic prophase and its loss leads to depletion of late prophase I spermatocytes through a p53-dependent apoptotic pathway. This phenotype is distinct from that observed in the DMC1 knockdown. Our meiotic knockdown and complementation system establishes an experimental platform for mechanistic studies of meiotic proteins with unknown functions or essential genes for which a testis-specific knockout is not possible.

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Teaser

Dai et al. develop an in vivo meiotic gene knockdown and protein complementation system to show that RAD51 has an essential role in mammalian meiosis. RAD51 loss in mouse testis leads to the depletion of late prophase I spermatocytes through a p53-dependent pathway.


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