title: Increased frequency of asynapsis and associated meiotic silencing of heterologous chromatin in the presence of irradiation-induced extra DNA double strand breaks.
abstract: In meiotic prophase of male placental mammals, the heterologous X and Y chromosomes remain largely unsynapsed, which activates meiotic sex chromosome inactivation (MSCI), leading to formation of the transcriptionally silenced XY body. MSCI is most likely related to meiotic silencing of unsynapsed chromatin (MSUC), a mechanism that can silence autosomal unsynapsed chromatin. However, heterologous synapsis and escape from silencing also occur. In mammalian species, formation of DNA double strand breaks (DSBs) during leptotene precedes meiotic chromosome pairing. These DSBs are essential to achieve full synapsis of homologous chromosomes. We generated 25% extra meiotic DSBs by whole body irradiation of mice. This leads to a significant increase in meiotic recombination frequency. In mice carrying translocation chromosomes with synaptic problems, we observed an approximately 35% increase in asynapsis and MSUC of the nonhomologous region in the smallest chromosome pair following irradiation. However, the same nonhomologous region in the largest chromosome pair, shows complete synapsis and escape from MSUC in almost 100% of the nuclei, irrespective of exposure to irradiation. We propose that prevention of synapsis and associated activation of MSUC is linked to the presence of unrepaired meiotic DSBs in the nonhomologous region. Also, spreading of synaptonemal complex formation from regions of homology may act as an opposing force, and drive heterologous synapsis.
authors.affiliation: Department of Reproduction and Development, Erasmus MC-University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Sam
authors.initials: S
authors.lastname: Schoenmakers
authors.forename: Evelyne
authors.initials: E
authors.lastname: Wassenaar
authors.forename: Wiggert A
authors.initials: WA
authors.lastname: van Cappellen
authors.forename: Alwin A
authors.initials: AA
authors.lastname: Derijck
authors.forename: Peter
authors.initials: P
authors.lastname: de Boer
authors.forename: Joop S E
authors.initials: JS
authors.lastname: Laven
authors.forename: J Anton
authors.initials: JA
authors.lastname: Grootegoed
authors.forename: Willy M
authors.initials: WM
authors.lastname: Baarends
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D023902:Chromosome Pairing; D003434:Crossing Over, Genetic; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D005720:Gamma Rays; D008297:Male; D049469:Meiotic Prophase I; D051379:Mice; D051135:Rad51 Recombinase / Q000378:metabolism
chemical_list: D002843:Chromatin; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse