Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase Journal Article

Authors: Wojtasz, L.; Daniel, K.; Roig, I.; Bolcun-Filas, E.; Xu, H.; Boonsanay, V.; Eckmann, C. R.; Cooke, H. J.; Jasin, M.; Keeney, S.; McKay, M. J.; Toth, A.
Article Title: Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase
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/SCcomponent 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. © 2009 Wojtasz et al.
Keywords: controlled study; unclassified drug; genetics; nonhuman; protein domain; protein localization; cell cycle protein; animal cell; mouse; synaptonemal complex; animal; meiosis; metabolism; mammalia; animals; cell cycle proteins; mice; animal tissue; mus; dna repair; protein depletion; animal experiment; protein interaction; enzyme activity; wild type; mice, inbred c57bl; c57bl mouse; correlation analysis; chromatin; nucleotide sequence; dna breaks, double-stranded; double stranded dna break; yeast; saccharomycetales; adenosine triphosphatase; chromosome protein; chromosome pairing; atr protein; adenosine triphosphatases; mutant; prophase; aaa atpase; hormad1 protein; hormad2 protein; trip13 protein; hormad2 protein, mouse; nohma protein, mouse; pachytene checkpoint 2 protein, mouse; synapse
Journal Title: PLoS Genetics
Volume: 5
Issue: 10
ISSN: 1553-7390
Publisher: Public Library of Science  
Date Published: 2009-10-01
Start Page: e1000702
Language: English
DOI: 10.1371/journal.pgen.1000702
PUBMED: 19851446
PROVIDER: scopus
PMCID: PMC2758600
Notes: --- - "Cited By (since 1996): 4" - "Export Date: 30 November 2010" - "Art. No.: e1000702" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Scott N Keeney
    113 Keeney
  2. Maria Jasin
    224 Jasin