Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase
Wojtasz, Lukasz (Technische Universität Dresden. Institute of Physiological Chemistry (Dresden, Alemanya))
Daniel, Katrin (Technische Universität Dresden. Institute of Physiological Chemistry (Dresden, Alemanya))
Roig, Ignasi, (Ignasi) dir. (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Bolcun-Filas, Ewelina (Cornell University (Nova York, Estats Units d'Amèrica))
Xu, Huiling (Peter MacCallum Cancer Centre (Melbourne, Austràlia))
Boonsanay, Verawan (Technische Universität Dresden. Institute of Physiological Chemistry (Dresden, Alemanya))
Eckmann, Christian R. (Max Planck Institute of Molecular Cell Biology and Genetics (Dresden, Alemanya))
Cooke, Howard J. (Western General Hospital (Edimburg, Escòcia))
Jasin, Maria (Memorial Sloan Kettering Cancer Center)
Keeney, Scott (Memorial Sloan Kettering Cancer Center)
McKay, Michael J. (Australian National University. Department of Radiation Oncology (Austràlia))
Toth, Attila (Technische Universität Dresden. Institute of Physiological Chemistry (Dresden, Alemanya))

Date:	2009
Abstract:	Meiotic crossovers are produced when programmed double-strand breaks (DSBs) are repaired by recombination from homologous chromosomes (homologues). In a wide variety of organisms, meiotic HORMA-domain proteins are required to direct DSB repair towards homologues. This inter-homologue bias is required for efficient homology search, homologue alignment, and crossover formation. HORMA-domain proteins are also implicated in other processes related to crossover formation, including DSB formation, inhibition of promiscuous formation of the synaptonemal complex (SC), and the meiotic prophase checkpoint that monitors both DSB processing and SCs. We examined the behavior of two previously uncharacterized meiosis-specific mouse HORMA-domain proteins-HORMAD1 and HORMAD2-in wild-type mice and in mutants defective in DSB processing or SC formation. HORMADs are preferentially associated with unsynapsed chromosome axes throughout meiotic prophase. We observe a strong negative correlation between SC formation and presence of HORMADs on axes, and a positive correlation between the presumptive sites of high checkpoint-kinase ATR activity and hyper-accumulation of HORMADs on axes. HORMADs are not depleted from chromosomes in mutants that lack SCs. In contrast, DSB formation and DSB repair are not absolutely required for depletion of HORMADs from synapsed axes. A simple interpretation of these findings is that SC formation directly or indirectly promotes depletion of HORMADs from chromosome axes. We also find that TRIP13 protein is required for reciprocal distribution of HORMADs and the SYCP1/SC-component along chromosome axes. Similarities in mouse and budding yeast meiosis suggest that TRIP13/Pch2 proteins have a conserved role in establishing mutually exclusive HORMAD-rich and synapsed chromatin domains in both mouse and yeast. Taken together, our observations raise the possibility that involvement of meiotic HORMA-domain proteins in the regulation of homologue interactions is conserved in mammals.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; Versió publicada
Subject:	Cell staining ; Homologous chromosomes ; Sex chromosomes ; Spermatocytes ; Chromosome staining ; Autosomes ; Meiosis
Published in:	PLoS Genetics, Vol. 5, N. 10 (October 2009) , p. e1000702, ISSN 1553-7404

DOI: 10.1371/journal.pgen.1000702
PMID: 19851446

28 p, 2.9 MB

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