Homeostatic control of recombination is implemented progressively in mouse meiosis
Open Access
- 4 March 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 14 (4), 424-430
- https://doi.org/10.1038/ncb2451
Abstract
Meiotic recombination involves the generation of double-strand breaks, that needs to be carefully controlled to avoid fetal aneuploidy. In worms and yeast, crossover numbers are constant regardless of the amount of double-strand breaks. Jasin and colleagues now show that such crossover homeostasis mechanisms exist at two stages in mammalian meiosis. Humans suffer from high rates of fetal aneuploidy, often arising from the absence of meiotic crossover recombination between homologous chromosomes1. Meiotic recombination is initiated by double-strand breaks (DSBs) generated by the SPO11 transesterase2. In yeast and worms, at least one buffering mechanism, crossover homeostasis, maintains crossover numbers despite variation in DSB numbers3,4,5,6,7,8. 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 gene—with correspondingly greater or fewer numbers of early recombination foci—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.Keywords
This publication has 46 references indexed in Scilit:
- ATM controls meiotic double-strand-break formationNature, 2011
- Molecular basis for enhancement of the meiotic DMC1 recombinase by RAD51 associated protein 1 (RAD51AP1)Proceedings of the National Academy of Sciences of the United States of America, 2011
- Comprehensive, Fine-Scale Dissection of Homologous Recombination Outcomes at a Hot Spot in Mouse MeiosisMolecular Cell, 2010
- Condensins Regulate Meiotic DNA Break Distribution, thus Crossover Frequency, by Controlling Chromosome StructureCell, 2009
- Global Analysis of the Meiotic Crossover LandscapeDevelopmental Cell, 2008
- High-resolution mapping of meiotic crossovers and non-crossovers in yeastNature, 2008
- The RIFLE criteria and mortality in acute kidney injury: A systematic reviewKidney International, 2008
- Crossover Homeostasis in Yeast MeiosisCell, 2006
- Two levels of interference in mouse meiotic recombinationProceedings of the National Academy of Sciences of the United States of America, 2006
- Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing overNature Genetics, 1996