Nature Genetics
18, 257 - 261 (1998)
doi:10.1038/ng0398-257
The meiotic checkpoint monitoring sypapsis eliminates spermatocytes via p53-independent apoptosisTeresa Odorisio1, 2, Tristan A. Rodriguez1, Edward P. Evans3, Alan R. Clarke4
& Paul S. Burgoyne1, 5
1Laboratory of Developmental Genetics, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
2Present address: Laboratorio di Biologia Molecolare e Cellulare, Istituto Dermopatico dell'Immacolata, Via dei Monti di Creta 104, 00167 Roma, Italy.
3MRC Mammalian Genetics Unit, Harwell, Didcot, OX11 ORD, UK.
4Department of Pathology, University Medical School, Teviot Place, Edinburgh EH8 9AG, UK.
5e-mail: pburgoy@nimr.mrc.ac.uk Evidence is accumulating that meiosis is subject to 'checkpoints' that monitor the quality of this complex process. In yeast unresolved double strand breaks (DSBs) in DNA are thought to trigger a 'recombination checkpoint' that leads to pachytene arrest1. In higher eukaryotes, there is evidence for a checkpoint that monitors chromosome synapsis and in mammals the most compelling evidence relates to the sex chromosomes2. In normal male mice, there is synapsis between the X and Y pseudoautosomal regions; in XSxr
aO mice, with a single asynaptic sex chromosome, there is arrest at the first meiotic metaphase3, the arrested cells being eliminated by apoptosis (our unpublished data). Satisfying the requirement for pseudoautosomal synapsis by providing a pairing partner for the XSxr
a chromosome avoids this arrest4. We have considered that this 'synapsis checkpoint' may be a modification of the yeast 'recombination checkpoint', with unresolved DSBs (a corollary of asynapsis) providing the trigger for apoptosis. DSBs induced by irradiation are known to trigger apoptosis in a number of cell types via a p53-dependent pathway5,6, and we now show that irradiation-induced spermatogonial apoptosis is also p53-dependent. In contrast, the apoptotic elimination of spermatocytes with synaptic errors proved to be p53-independent.
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