Homeostatic control of recombination is implemented progressively in mouse meiosis

Francesca Cole, Liisa Kauppi, Julian Lange, Ignasi Roig, Raymond Wang, Scott Keeney, Maria Jasin

Research output: Contribution to journalArticleResearchpeer-review

126 Citations (Scopus)

Abstract

Humans suffer from high rates of fetal aneuploidy, often arising from the absence of meiotic crossover recombination between homologous chromosomes. Meiotic recombination is initiated by double-strand breaks (DSBs) generated by the SPO11 transesterase. In yeast and worms, at least one buffering mechanism, crossover homeostasis, maintains crossover numbers despite variation in DSB numbers. We show here that mammals exhibit progressive homeostatic control of recombination. In wild-type mouse spermatocytes, focus numbers for early recombination proteins (RAD51, DMC1) were highly variable from cell to cell, whereas foci of the crossover marker MLH1 showed little variability. Furthermore, mice with greater or fewer copies of the Spo11 geneg-with correspondingly greater or fewer numbers of early recombination focig-exhibited relatively invariant crossover numbers. Homeostatic control is enforced during at least two stages, after the formation of early recombination intermediates and later while these intermediates mature towards crossovers. Thus, variability within the mammalian meiotic program is robustly managed by homeostatic mechanisms to control crossover formation, probably to suppress aneuploidy. Meiotic recombination exemplifies how order can be progressively implemented in a self-organizing system despite natural cell-to-cell disparities in the underlying biochemical processes. © 2012 Macmillan Publishers Limited. All rights reserved.
Original languageEnglish
Pages (from-to)424-430
JournalNature Cell Biology
Volume14
DOIs
Publication statusPublished - 1 Apr 2012

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