Knockout mice provide novel insights into meiotic chromosome and telomere dynamics.
Meiosis is a succession of two specialized cell divisions that leads to the formation of gametes and thereby compensates for genome doubling at fertilization. During the extended prophase of the first meiotic division chromosomes assemble protein cores (axial elements) that attach their ends to the nuclear envelope. These ends transiently gather at a limited sector of the nuclear periphery (bouquet stage) at a time when meiotic recombination is initiated and when chromosomes initiate stable pairing (synapsis). This review discusses novel insights into the relation between recombinational DNA repair and meiotic telomere dynamics that have arrived from recent studies of transchromosomal mice and knockout mice. Analysis of mice deficient for A-type lamins, histone H2AX, Suv39h HMTases, and the AE protein SYCP3 suggests that entry into prophase I requires heterochromatin integrity and lamin A expression. Initiation of meiotic telomere clustering represents an early recombination-independent event in first meiotic prophase, while exit from the bouquet stage depends on signals that emanate from the progress of recombinational DNA repair as sensed by ATM kinase and relayed through histone H2AX.
Scherthan
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Max-Planck-Institut für Molekulare Genetik, Berlin, Germany. scherth@web.de
D000818:Animals; D018797:Cell Cycle Proteins; D002843:Chromatin / Q000648:ultrastructure; D023902:Chromosome Pairing; D033481:Chromosomes, Mammalian / Q000648:ultrastructure*; D004260:DNA Repair; D004268:DNA-Binding Proteins; D006657:Histones / Q000235:genetics / Q000502:physiology; D008297:Male; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D009685:Nuclear Envelope / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid; D013091:Spermatogenesis; D013094:Spermatozoa / Q000378:metabolism / Q000648:ultrastructure*; D016615:Telomere / Q000737:chemistry / Q000648:ultrastructure*
D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; C490062:Sycp3 protein, mouse; C475961:gamma-H2AX protein, mouse