title: Mutations that affect meiosis in male mice influence the dynamics of the mid-preleptotene and bouquet stages.
abstract: Meiosis pairs and segregates homologous chromosomes and thereby forms haploid germ cells to compensate the genome doubling at fertilization. Homologue pairing in many eukaryotic species depends on formation of DNA double strand breaks (DSBs) during early prophase I when telomeres begin to cluster at the nuclear periphery (bouquet stage). By fluorescence in situ hybridization criteria, we observe that mid-preleptotene and bouquet stage frequencies are altered in male mice deficient for proteins required for recombination, ubiquitin conjugation and telomere length control. The generally low frequencies of mid-preleptotene spermatocytes were significantly increased in male mice lacking recombination proteins SPO11, MEI1, MLH1, KU80, ubiquitin conjugating enzyme HR6B, and in mice with only one copy of the telomere length regulator Terf1. The bouquet stage was significantly enriched in Atm(-/-), Spo11(-/-), Mei1(m1Jcs/m1Jcs), Mlh1(-/-), Terf1(+/-) and Hr6b(-/-) spermatogenesis, but not in mice lacking recombination proteins DMC1 and HOP2, the non-homologous end-joining DNA repair factor KU80 and the ATM downstream effector GADD45a. Mice defective in spermiogenesis (Tnp1(-/-), Gmcl1(-/-), Asm(-/-)) showed wild-type mid-preleptotene and bouquet frequencies. A low frequency of bouquet spermatocytes in Spo11(-/-)Atm(-/-) spermatogenesis suggests that DSBs contribute to the Atm(-/-)-correlated bouquet stage exit defect. Insignificant changes of bouquet frequencies in mice with defects in early stages of DSB repair (Dmc1(-/-), Hop2(-/-)) suggest that there is an ATM-specific influence on bouquet stage duration. Altogether, it appears that several pathways influence telomere dynamics in mammalian meiosis.
authors.affiliation: Max-Planck-Inst. for Molecular Genetics, Ihnestr. 73, D-14195 Berlin, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Liebe
authors.forename: G
authors.initials: G
authors.lastname: Petukhova
authors.forename: M
authors.initials: M
authors.lastname: Barchi
authors.forename: M
authors.initials: M
authors.lastname: Bellani
authors.forename: H
authors.initials: H
authors.lastname: Braselmann
authors.forename: T
authors.initials: T
authors.lastname: Nakano
authors.forename: T K
authors.initials: TK
authors.lastname: Pandita
authors.forename: M
authors.initials: M
authors.lastname: Jasin
authors.forename: A
authors.initials: A
authors.lastname: Fornace
authors.forename: M L
authors.initials: ML
authors.lastname: Meistrich
authors.forename: W M
authors.initials: WM
authors.lastname: Baarends
authors.forename: J
authors.initials: J
authors.lastname: Schimenti
authors.forename: T
authors.initials: T
authors.lastname: de Lange
authors.forename: S
authors.initials: S
authors.lastname: Keeney
authors.forename: R D
authors.initials: RD
authors.lastname: Camerini-Otero
authors.forename: H
authors.initials: H
authors.lastname: Scherthan
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004706:Endodeoxyribonucleases; D004950:Esterases / Q000172:deficiency / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D011418:Prophase / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics; D011995:Recombination, Genetic; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics; D016615:Telomere / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics; D000099257:Meiotic Recombination Protein SPO11
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases; D004950:Esterases; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; D000099257:Meiotic Recombination Protein SPO11; C576325:Atm protein, mouse