title: Presence of an extra chromosome alters meiotic double-stranded break repair dynamics and MLH1 foci distribution in human oocytes.
abstract: Studies performed on human trisomic 21 oocytes have revealed that during meiosis, the three homologues 21 synapse and, in some cases, achieve what looks like a trivalent. This implies that meiotic recombination takes place among the three homologous chromosomes 21, and to some extent, crossovers form between them. To see how meiotic recombination is in the presence of an extra chromosome 21, we analyzed the distribution of three recombination markers (γH2AX, RPA, and MLH1) on trisomic 21 oocytes at pachynema and, in particular, on chromosomes 21. Results clearly show how the presence of an extra chromosome 21 alters meiotic recombination progression, leading to the presence of a higher number of early recombination markers at pachynema. Moreover, the distribution on these chromosomes 21 of some of these markers is different in aneuploid oocytes. Finally, there is a substantial increase in the number of MLH1 foci, a marker of most crossovers in mammals, which is related to the number of synapsed chromosomes in pachynema. Thus, bivalents 21 had fewer MLH1 foci than partial or total trivalents, suggesting a close relationship between synapsis and crossover designation. All of the data presented suggest that the presence of an extra chromosome alters meiotic recombination globally in aneuploid human oocytes.
authors.affiliation: Departament Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, 08193, Bellaterra, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Robles
authors.forename: I
authors.initials: I
authors.lastname: Roig
authors.forename: R
authors.initials: R
authors.lastname: Garcia
authors.forename: M
authors.initials: M
authors.lastname: Brieño-Enríquez
authors.forename: M
authors.initials: M
authors.lastname: Martin
authors.forename: Ll
authors.initials: L
authors.lastname: Cabero
authors.forename: N
authors.initials: N
authors.lastname: Toran
authors.forename: M
authors.initials: M
authors.lastname: Garcia Caldés
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D023902:Chromosome Pairing / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008540:Meiosis / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D009865:Oocytes / Q000166:cytology*; D049471:Pachytene Stage / Q000235:genetics; D013573:Synaptonemal Complex / Q000235:genetics; D014314:Trisomy / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1