The EMBO Journal (2010) 29, 586–596 | & 2010 European Molecular Biology Organization | Some Rights Reserved 0261-4189/10 www.embojournal.org Yeast axial-element protein, Red1, binds SUMO chains to promote meiotic interhomologue recombination and chromosome synapsis THE EMBO JOURNAL EMBO open This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without speciﬁc permission. Feng-Ming Lin1,2, Yi-Ju Lai1,2, Hui-Ju Shen2, Yun-Hsin Cheng2 and Ting-Fang Wang1,2,* 1Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan and 2Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan The synaptonemal complex (SC) is a tripartite protein structure consisting of two parallel axial elements (AEs) and a central region. During meiosis, the SC connects paired homologous chromosomes, promoting interhomo- logue (IH) recombination. Here, we report that, like the CE component Zip1, Saccharomyces cerevisiae axial-element structural protein, Red1, can bind small ubiquitin-like modiﬁer (SUMO) polymeric chains. The Red1–SUMO chain interaction is dispensable for the initiation of meio- tic DNA recombination, but it is essential for Tel1- and Mec1-dependent Hop1 phosphorylation, which ensures IH recombination by preventing the inter-sister chromatid DNA repair pathway. Our results also indicate that Red1 and Zip1 may directly sandwich the SUMO chains to mediate SC assembly. We suggest that Red1 and SUMO chains function together to couple homologous recombi- nation and Mec1–Tel1 kinase activation with chromosome synapsis during yeast meiosis. The EMBO Journal (2010) 29, 586–596. doi:10.1038/ emboj.2009.362; Published online 3 December 2009 Subject Categories: cell cycle; genome stability & dynamics Keywords: DNA recombination; meiosis; Red1; SUMO; synaptonemal complex Introduction Crossing-over between homologous chromosomes ensures accurate segregation during the ﬁrst meiotic division. Homologous chromosomes must ﬁrst be linked by chiasmata, the cytological manifestation of crossover (CO) recombina- tion products that are established during meiotic prophase. Meiotic recombination is initiated by developmentally pro- grammed DNA double-strand breaks (DSBs), the formation of which requires the products of at least 10 genes, including SPO11 (Keeney, 2001). These DSBs are then resected by the *Corresponding author. Institute of Molecular Biology, Academia Sinica, 128 Academia Road, Nankang, Taipei 11529, Taiwan. Tel.: þ 886 2 2789 9188; Fax: þ 886 2 2782 6085; E-mail: tfwang@gate.sinica.edu.tw Received: 8 June 2009; accepted: 28 October 2009; published online: 3 December 2009 586 The EMBO Journal VOL 29 | NO 3 | 2010 Mre11-Rad50-Xrs2 nuclease to generate 30 single-strand tails that invade the intact DNA duplexes used in DNA repair (Neale et al, 2005). Most of these events use homologous chromosomes, not sister chromatids, as the templates in DNA repair, yielding CO and non-CO (NCO) products (for a review see Bishop and Zickler, 2004). Two kinds of CO are seen in Saccharomyces cerevisiae. The ﬁrst CO class is randomly distributed along the chromosomes and requires Mus81- Mms4 endonuclease (de los Santos et al, 2003; Borner et al, 2004; Lynn et al, 2007). The second CO class is distance- dependent and requires ZMM proteins (an acronym for yeast proteins Zip1-4, Msh4-5 and Mer3; Borner et al, 2004) at CO- designated sites to stabilise early recombination intermedi- ates against the action of the anti-CO helicase Sgs1 (Jessop et al, 2006; Oh et al, 2007, 2008; Jessop and Lichten, 2008). The ZMM proteins also form a zipper-like proteinaceous structure between homologous chromosomes, known as the synaptonemal complex (SC), during the zygotene and pachy- tene stages. These structures include a major SC component (Zip1) and the SC initiating or elongating proteins (Zip2-4, Mer3, Msh4-5 and Spo16) (Sym et al, 1993; Hollingsworth et al, 1995; Chua and Roeder, 1998; Agarwal and Roeder, 2000; Novak et al, 2001; Borner et al, 2004; Fung et al, 2004; Perry et al, 2005; Tsubouchi et al, 2006; Shinohara et al, 2008). The SC consists of a central region and two dense lateral elements. The lateral element constitutes the rod-like homologue axis, which is called an axial element (AE) before synapsis. The chromatin loops of sister chromatids are orga- nised along the axis. The central region contains transverse ﬁlaments (TFs) oriented perpendicularly to the longitudinal axis of the SC, resulting in the striated, zipper-like appear- ance of the SC (Henderson and Keeney, 2005). The compo- nents of the yeast AE include sister chromatid cohesin complexes (e.g., Rec8), DNA topoisomerase II (Top2) and a few meiosis-speciﬁc proteins (e.g., Red1, Hop1 and Mek1) (Hollingsworth and Ponte, 1997; Smith and Roeder, 1997; Klein et al, 1999; Blat et al, 2002; Page and Hawley, 2004). Mek1 is a serine–threonine protein kinase that functions in combination with Red1 and Hop1 to ensure interhomologue (IH) recombination by preventing the use of a sister chromatid as the template in DNA repair (Bailis and Roeder, 1998; Wan et al, 2004; Niu et al, 2005, 2007). Mek1 kinase activity is dependant on Hop1 phosphorylation, which is mediated by Mec1 and Tel1, yeast homologues of the mammalian ATR and ATM kinases (Carballo et al, 2008). Hop1 protein has been shown to interact with DNA in vitro (Kironmai et al, 1998) and to interact with itself and Red1 (Bailis and Roeder, 1998; de los Santos and Hollingsworth, 1999; Woltering et al, 2000). Hop1 also promotes dimerisation of Mek1 (Niu et al, 2005). Red1 is & 2010 European Molecular Biology Organization