Female-specific features of recombinational double-stranded DNA repair in relation to synapsis and telomere dynamics in human oocytes |
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Authors: | I?Roig B?Liebe J?Egozcue Ll?Cabero Email author" target="_blank">M?GarciaEmail author Email author" target="_blank">H?ScherthanEmail author |
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Institution: | (1) Dept. de Biol. Cellular, Fisiologia i Immunologia, Univ. Autònoma de Barcelona, 08193 Bellaterra, Spain;(2) Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany;(3) Servei de Ginecologia i Obstetrícia, Hospital Materno-Infantil de la Vall d Hebron, Barcelona, Spain;(4) Inst. for Radiation Biology Bundeswehr, Neuherbergstrasse 11, 80937 Munich, Germany |
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Abstract: | Chromosome segregation errors are a significant cause of aneuploidy among human neonates and often result from errors in female meiosis that occur during fetal life. For the latter reason, little is known about chromosome dynamics during female prophase I. Here, we analyzed chromosome reorganization, and centromere and telomere dynamics in meiosis in the human female by immunofluorescent staining of the SYCP3 and SYCP1 synaptonemal complex proteins and the course of recombinational DNA repair by IF of phospho-histone H2A.X ( -H2AX), RPA and MLH1 recombination proteins. We found that SYCP3, but not SYCP1, aggregates appear in the preleptotene nucleus and some persist up to pachytene. Telomere clustering (bouquet stage) in oocytes lasted from late-leptotene to early pachytene—significantly longer than in the male. Leptotene and zygotene oocytes and spermatocytes showed strong -H2AX labeling, while -H2AX patches, which colocalized with RPA, were present on SYCP1-tagged pachytene SCs. This was rarely seen in the male and may suggest that synapsis installs faster with respect to progression of recombinational double-strand break repair or that the latter is slower in the female. It is speculated that the presence of -H2AX into pachytene highlights female-specific peculiarities of recombination, chromosome behavior and checkpoint control that may contribute to female susceptibility for aneuploidy.I. Roig and B. Liebe made an equal contribution to this work |
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