Leptotene/Zygotene Chromosome Movement Via the SUN/KASH Protein Bridge in Caenorhabditis elegans Antoine Baudrimont 1 , Alexandra Penkner 1 , Alexander Woglar 1 , Thomas Machacek 1 , Christina Wegrostek 1 , Jiradet Gloggnitzer 1¤ , Alexandra Fridkin 2 , Franz Klein 1 , Yosef Gruenbaum 2 , Pawel Pasierbek 3,4 , Verena Jantsch 1 * 1 Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria, 2 Department of Genetics, Hebrew University, Jerusalem, Israel, 3 Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria, 4 Institute of Molecular Pathology, Vienna, Austria Abstract The Caenorhabditis elegans inner nuclear envelope protein matefin/SUN-1 plays a conserved, pivotal role in the process of genome haploidization. CHK-2–dependent phosphorylation of SUN-1 regulates homologous chromosome pairing and interhomolog recombination in Caenorhabditis elegans. Using time-lapse microscopy, we characterized the movement of matefin/SUN-1::GFP aggregates (the equivalent of chromosomal attachment plaques) and showed that the dynamics of matefin/SUN-1 aggregates remained unchanged throughout leptonene/zygotene, despite the progression of pairing. Movement of SUN-1 aggregates correlated with chromatin polarization. We also analyzed the requirements for the formation of movement-competent matefin/SUN-1 aggregates in the context of chromosome structure and found that chromosome axes were required to produce wild-type numbers of attachment plaques. Abrogation of synapsis led to a deceleration of SUN-1 aggregate movement. Analysis of matefin/SUN-1 in a double-strand break deficient mutant revealed that repair intermediates influenced matefin/SUN-1 aggregate dynamics. Investigation of movement in meiotic regulator mutants substantiated that proper orchestration of the meiotic program and effective repair of DNA double-strand breaks were necessary for the wild-type behavior of matefin/SUN-1 aggregates. Citation: Baudrimont A, Penkner A, Woglar A, Machacek T, Wegrostek C, et al. (2010) Leptotene/Zygotene Chromosome Movement Via the SUN/KASH Protein Bridge in Caenorhabditis elegans. PLoS Genet 6(11): e1001219. doi:10.1371/journal.pgen.1001219 Editor: Monica Colaia ´covo, Harvard University, United States of America Received April 23, 2010; Accepted October 25, 2010; Published November 24, 2010 Copyright: ß 2010 Baudrimont et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by grants from the FWF (V11B12, P-21107, SFB-F34, ‘‘Chromosome Dynamics’’), the WWTF (LS05009), the University of Vienna (IO31-B), an Israel Science Foundation (ISF) grant to YG, and a Clore scholarship to AF. The Caenorhabditis Genetics Center is funded by the NIH National Canter for Research Resources (NCRR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: verena.jantsch@univie.ac.at ¤ Current address: Gregor Mendel Institute of Molecular Plant Biology, Austrian Academy of Sciences, Vienna, Austria Introduction During the first meiotic division, homologous parental chro- mosomes must accomplish numerous tasks that eventually result in their connection via homologous recombination. They must recognize one another, align, synapse via the tripartite proteina- ceous synaptonemal complex (SC), and repair programmed double-strand breaks (DSBs); a subset of DSBs is repaired using the homologous partner as a template [1]. During this period, the chromosomes are connected to the nuclear envelope at one or both ends [2]. The highly conserved protein interaction module of SUN/KASH domain proteins has emerged as a core element for the attachment of chromosomal ends to the nuclear envelope, and for telomere-led chromosomal movement. The mechanism for moving chromosomes during early prophase I inside the nucleus via the SUN/KASH bridge, which provides a connection to various cytoskeletal forces in the cytoplasm, appears to be a general, evolutionarily conserved phenomenon (for reviews see [3– 5]). Studies in Saccharomyces cerevisiae [6,7], Schizosaccharomyces pombe [8], and maize [9] discovered differences among organisms with regard to which factors are employed to build the connection of the chromosome ends to the SUN-domain proteins in the inner nuclear envelope, and which cytoskeletal forces drive the movement. For example, in S. cerevisiae, telomere-led chromosome movement has been observed during meiotic prophase I, from leptotene to pachytene [6,7,10]. Interference with prophase chromosome movement in S. cerevisiae results in delayed pairing and DSB processing, aberrant crossover formation, and loss of crossover interference [6,7,11–16]. In many organisms, formation of the synaptonemal complex requires the formation of programmed meiotic DSBs; however, in C. elegans, synapsis is independent of DSBs [17]. In C. elegans, the SC is comprised of the lateral element components HTP-1 to 3 and HIM-3, and the central region components SYP-1 to SYP-4 [18,19]. HTP-1, in addition to being part of the lateral element, also plays a role in licensing synapsis [20,21]. Another characteristic of C. elegans is that the pairing of homologs involves homolog recognition regions (HRRs), also called pairing center (PC) regions, which are enriched in heterochromatic repeats localized at one end of each chromosome. HRRs were shown to be required to initiate the subsequent key features of meiosis I, recombination and disjunction [22–24]. The PC proteins ZIM-1 to ZIM-3 and HIM-8 bind to HRRs, and specifically localize to either one or two chromosomes [25–27]. When extrachromosomal arrays of the heterochromatic repeats found in HRRs are introduced into C. elegans germline cells, they PLoS Genetics | www.plosgenetics.org 1 November 2010 | Volume 6 | Issue 11 | e1001219