title: ATR, BRCA1 and gammaH2AX localize to unsynapsed chromosomes at the pachytene stage in human oocytes.
abstract: Asynapsis of homologous chromosomes at the pachytene stage has been associated with gametogenic failure and infertility, but the cellular mechanisms involved are currently unknown in human meiocytes. In mice, the protein encoded by the breast-cancer susceptibility gene Brca1 has been described to direct kinase ATR (ataxia telangiectasia and Rad3 related) to any unpaired DNA at the pachytene stage, where ATR triggers H2AX phosphorylation, resulting in the silencing of those chromosomes. In this study, the distribution of ATR, BRCA1 and the phosphorylated histone gammaH2AX is assessed by immunofluorescence in human oocytes and it is found that they localize at unpaired chromosomes at the pachytene stage. Evidence is shown to propose that BRCA1, ATR and gammaH2AX in the human may be part of a system such as the one previously described in mouse, which signals unsynapsed chromosomes at pachytene and may lead to their silencing.
authors.affiliation: Departament de Biologia Cellular, Unitat de Biologia Cellular i Genètica Mèdica, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Garcia-Cruz
authors.forename: I
authors.initials: I
authors.lastname: Roig
authors.forename: P
authors.initials: P
authors.lastname: Robles
authors.forename: H
authors.initials: H
authors.lastname: Scherthan
authors.forename: M
authors.initials: M
authors.lastname: Garcia Caldés
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D019313:BRCA1 Protein / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D023902:Chromosome Pairing / Q000502:physiology; D002877:Chromosomes, Human / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D020868:Gene Silencing / Q000502:physiology; D018392:Genomic Imprinting / Q000502:physiology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D009865:Oocytes / Q000378:metabolism*; D049471:Pachytene Stage; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D018797:Cell Cycle Proteins; C468783:H2AX protein, human; D006657:Histones; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases