A new role for SPO11 during mouse spermatogenesis

Abstract

Synapsis of the paired homologs and recombination are prerequisites for accuratechromosome segregation in meiosis. It is not clear whether there is a homology dependent mechanism that brings homologs together before double‐strand breaks (DSBs) initiate recombination in prophase. We are currently investigating the existence of homologous chromosomal pairing in mammalian premeiotic (spermatogonia) and meiotic S‐phase. Our data so far suggest that a significant level of pairing occurs in cells in meiotic S–phase (preleptotene mouse spermatocytes) as assessed by both interstitial and sub‐telomeric chromosome specific FISH probes. Taking advantage of a mouse expressing a catalytic mutant of SPO11, we show that this pairing requires SPO11, but is independent of its DSB activity, consistent with a previous report in budding yeast (Cha et al. (2000) Genes and Development 14: 493). This is the first report of such potential early functions of SPO11 in mammals. We also demonstrate that early pairing may require the nuclear membrane protein SUN1, important for telomere attachment to the nuclear membrane and gametogenesis (Ding X. et. al. (2007) Dev Cell 12:863–872; Chi Y. et. al. (2009) Development 136:965–973 ) and that SUN1 may directly interact with SPO11. Although the generation of DSB is normal in Sun1−/− mice, pairing and synapsis are impaired during meiotic prophase. Our observation that preleptotene homologous pairing is also disrupted in Sun1−/− mice suggests that this phenomenon is not required for the generation of SPO11 mediated DSBs.