title: Programmed phosphorylation of histone H2AX precedes a phase of DNA double-strand break-independent synapsis in mouse meiosis.
abstract: Accurate homologue synapsis during meiosis is essential for faithful chromosome segregation and formation of viable gametes. The finding of Spo11-dependent gamma-H2AX (γH2AX) formation during leptotene and data on mutant mice have led to the notion that synapsis in mammals depends on meiotic DNA double-stranded break (DSB) repair. A second wave of ataxia telangiectasia mutated (ATM) and Rad3-related (ATR)-dependent γH2AX formation has been observed in Atm-null mice during zygotene, suggesting that this wave of phosphorylation also occurs in normal mice. Here I aimed to confirm and to analyse in deep this wave of phosphorylation. Immunostaining of spread spermatocytes shows that γH2AX accumulates on the short last axis stretches to pair. This accumulation appears within all the nuclei undergoing a specific step of late zygotene and disappears from every spermatocyte immediately after pairing completion. This γH2AX signal co-localises with ATR, is Spo11-independent and does not co-localise with free DNA 3'-end labelling. I conclude that ATR/γH2AX asynapsis signalling at the end of zygotene belongs to a physiologically programmed pathway operating at a specific meiotic step, and I propose that this pathway is involved in the triggering of a phase of DSB-independent chromosome pairing that leads to synapsis completion in normal mouse meiosis.
authors.affiliation: Departamento de Biología Celular, Facultad de Medicina, Universidad de Valladolid, Ramón y Cajal 7, 47005 Valladolid, Spain. jblanco@med.uva.es
authors.forename: Josefa
authors.initials: J
authors.lastname: Blanco-Rodríguez
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D023902:Chromosome Pairing; D053903:DNA Breaks, Double-Stranded; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008297:Male; D049469:Meiotic Prophase I; D051379:Mice; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013090:Spermatocytes / Q000378:metabolism*; D000099257:Meiotic Recombination Protein SPO11
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004706:Endodeoxyribonucleases; D006657:Histones; D017346:Protein Serine-Threonine Kinases; D000099257:Meiotic Recombination Protein SPO11; C576897:Atr protein, mouse; C475961:gamma-H2AX protein, mouse