title: The meiotic checkpoint monitoring synapsis eliminates spermatocytes via p53-independent apoptosis.
abstract: 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 arrest. In higher eukaryotes, there is evidence for a checkpoint that monitors chromosome synapsis and in mammals the most compelling evidence relates to the sex chromosomes. In normal male mice, there is synapsis between the X and Y pseudoautosomal regions; in XSxr(a)O mice, with a single asynaptic sex chromosome, there is arrest at the first meiotic metaphase, the arrested cells being eliminated by apoptosis (our unpublished data).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 arrest. 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 pathway, 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.
authors.affiliation: Laboratory of Developmental Genetics, National Institute for Medical Research, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Odorisio
authors.forename: T A
authors.initials: TA
authors.lastname: Rodriguez
authors.forename: E P
authors.initials: EP
authors.lastname: Evans
authors.forename: A R
authors.initials: AR
authors.lastname: Clarke
authors.forename: P S
authors.initials: PS
authors.lastname: Burgoyne
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000528:radiation effects; D002869:Chromosome Aberrations; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D005260:Female; D016158:Genes, p53; D008297:Male; D008540:Meiosis; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D013090:Spermatocytes / Q000502:physiology*; D013573:Synaptonemal Complex / Q000235:genetics; D013737:Testis / Q000473:pathology / Q000528:radiation effects; D014916:Whole-Body Irradiation; D014960:X Chromosome; D014998:Y Chromosome