THE MEIOTIC CHECKPOINT MONITORING SYNAPSIS ELIMINATES SPERMATOCYTES VIA P53-INDEPENDENT APOPTOSIS

Evidence is accumulating that meiosis is subject to 'checkpoints' that monitor the quality of this complex process. In yeast, unresolved dou ble strand breaks (DSBs) in DNA are thought to trigger a 'recombinatio n checkpoint' that leads to pachytene arrest(1). In higher eukaryotes, there is evidence for a checkpoint that monitors chromosome synapsis and in mammals the most compelling evidence relates to the sex chromos omes(2). In normal male mice, there is synapsis between the X and Y ps eudoautosomal regions; in XSxr(a)O mice, with a single asynaptic sex c hromosome, there is arrest at the first meiotic metaphase(3), the arre sted cells being eliminated by apoptosis (our unpublished data). Satis fying the requirement for pseudoautosomal synapsis by providing a pair ing partner for the XSxr(a) chromosome avoids this arrest(4). We have considered that this 'synapsis checkpoint' may be a modification of th e yeast 'recombination checkpoint', with unresolved DSBs (a corollary of asynapsis) providing the trigger for apoptosis. DSBs induced by irr adiation are known to trigger apoptosis in a number of cell types via a p53-dependent pathway(5,6), and we now show that irradiation-induced spermatogonial apoptosis is also p53-dependent. In contrast, the apop totic elimination of spermatocytes with synaptic errors proved to be p 53-independent.