The fundamental function of meiosis, segregation of the maternal and paternal chromosomes, is facilitated by reciprocal recombination and intimate juxtaposition (synapsis) between the homologous chromosomes in meiotic prophase. Homolog synapsis, mediated by the synaptonemal complex (SC), is preceded by a stage of pairing between the centromeres of nonhomologous chromosomes. This pairing, named nonhomologous centromere coupling (NCC), depends upon the meiotic cohesin Rec8 and the SC protein Zip1. Nonhomologously coupled centromeres (NCCs), if remain tethered, must interfere with complete homolog synapsis (SC formation). Recent experiments demonstrate the existence of a mechanism that regulates NCC. Importantly, this is part of a regulatory network which couples dissolution of the NCCs with SC formation between the homologous chromosomes, thereby ensuring appropriate meiotic chromosome interactions. This paper reviews this network and presents speculations relating to the initiation of SC formation at centromere. 1. Introduction Cell biologists working on meiosis, the cell division that segregates the maternal and paternal chromosomes to produce haploid gametes from diploid parent cells, have ever been fascinated by the ballet between chromosomes that occupy a substantial part of the meiotic prophase (reviewed in [1, 2]). This culminates into initial side-by-side alignment (named pairing) of the two homologous chromosomes, which subsequently converts to intimate physical juxtaposition (named synapsis) of the two homologs along their entire length. Synapsis between the homologous chromosomes is mediated by a complex proteinaceous structure named synaptonemal complex (SC). (SC may also form between nonhomologous chromosomes or segments of chromosomes that are not homologous.) The SC is a tripartite organelle in which a central element (CE) connects two lateral elements (LEs); each LE represents the merged axes formed along the length of the two sister chromatids (reviewed in [3]). In many organisms, homolog synapsis and SC formation are stringently coupled with the programmed induction of meiotic DNA double strand-breaks (DSBs) by the conserved topoisomerase Spo11, which initiates the process of reciprocal interhomolog recombination (reviewed in [4]). A twist in the tale came from the Roeder laboratory [5]. It was demonstrated that, in budding yeast strain lacking Spo11, a stage of pairing, named Nonhomologous Centromere Coupling (NCC), between the centromeres of nonhomologous chromosomes precedes the homology-dependent synapsis. (The nonhomologously
References
[1]
G. S. Roeder, “Meiotic chromosomes: it takes two to tango,” Genes and Development, vol. 11, no. 20, pp. 2600–2621, 1997.
[2]
R. Koszul and N. Kleckner, “Dynamic chromosome movements during meiosis: a way to eliminate unwanted connections?” Trends in Cell Biology, vol. 19, no. 12, pp. 716–724, 2009.
[3]
S. L. Page and R. S. Hawley, “The genetics and molecular biology of the synaptonemal complex,” Annual Review of Cell and Developmental Biology, vol. 20, pp. 525–558, 2004.
[4]
D. Zickler and N. Kleckner, “Meiotic chromosomes: integrating structure and function,” Annual Review of Genetics, vol. 33, pp. 603–754, 1999.
[5]
T. Tsubouchi and G. S. Roeder, “A synaptonemal complex protein promotes homology-independent centromere coupling,” Science, vol. 308, no. 5723, pp. 870–873, 2005.
[6]
A. Bardhan, H. Chuong, and D. S. Dawson, “Meiotic cohesin promotes pairing of nonhomologous centromeres in early meiotic prophase,” Molecular Biology of the Cell, vol. 21, no. 11, pp. 1799–1809, 2010.
[7]
D. Obeso and D. S. Dawson, “Temporal characterization of homology-independent centromere coupling in meiotic prophase,” PLoS ONE, vol. 5, no. 4, Article ID e10336, 2010.
[8]
J. E. Falk, A. C. H. Chan, E. Hoffmann, and A. Hochwagen, “A Mec1- and PP4-Dependent checkpoint couples centromere pairing to meiotic recombination,” Developmental Cell, vol. 19, no. 4, pp. 599–611, 2010.
[9]
M. Sym, J. A. Engebrecht, and G. S. Roeder, “ZIP1 is a synaptonemal complex protein required for meiotic chromosome synapsis,” Cell, vol. 72, no. 3, pp. 365–378, 1993.
[10]
K. S. Tung and G. S. Roeder, “Meiotic chromosome morphology and behavior in zip1 mutants of Saccharomyces cerevisiae,” Genetics, vol. 149, no. 2, pp. 817–832, 1998.
[11]
H. Dong and G. S. Roeder, “Organization of the yeast Zip1 protein within the central region of the synaptonemal complex,” Journal of Cell Biology, vol. 148, no. 3, pp. 417–426, 2000.
[12]
C. H. Cheng, Y. H. Lo, S. S. Liang et al., “SUMO modifications control assembly of synaptonemal complex and polycomplex in meiosis of Saccharomyces cerevisiae,” Genes and Development, vol. 20, no. 15, pp. 2067–2081, 2006.
[13]
F. M. Lin, Y. J. Lai, H. J. Shen, Y. H. Cheng, and T. F. Wang, “Yeast axial-element protein, Red1, binds SUMO chains to promote meiotic interhomologue recombination and chromosome synapsis,” EMBO Journal, vol. 29, no. 3, pp. 586–596, 2010.
[14]
C. S. Eichinger and S. Jentsch, “Synaptonemal complex formation and meiotic checkpoint signaling are linked to the lateral element protein Red1,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 25, pp. 11370–11375, 2010.
[15]
J. A. Ubersax, E. L. Woodbury, P. N. Quang et al., “Targets of the cyclin-dependent kinase Cdk1,” Nature, vol. 425, no. 6960, pp. 859–864, 2003.
[16]
P. Jordan, A. Copsey, L. Newnham, E. Kolar, M. Lichten, and E. Hoffmann, “Ipl1/Aurora B kinase coordinates synaptonemal complex disassembly with cell cycle progression and crossover formation in budding yeast meiosis,” Genes and Development, vol. 23, no. 18, pp. 2237–2251, 2009.
[17]
Z. Zhu, S. Mori, H. Oshiumi, K. Matsuzaki, M. Shinohara, and A. Shinohara, “Cyclin-dependent kinase promotes formation of the synaptonemal complex in yeast meiosis,” Genes to Cells, vol. 15, no. 10, pp. 1036–1050, 2010.
[18]
R. K. Clyne, V. L. Katis, L. Jessop et al., “Polo-like kinase Cdc5 promotes chiasmata formation and cosegregation of sister centromeres at meiosis I,” Nature Cell Biology, vol. 5, no. 5, pp. 480–485, 2003.
[19]
A. Sourirajan and M. Lichten, “Polo-like kinase Cdc5 drives exit from pachytene during budding yeast meiosis,” Genes and Development, vol. 22, no. 19, pp. 2627–2632, 2008.
[20]
G. A. Brar, A. Hochwagen, L. S. S. Ee, and A. Amon, “The multiple roles of cohesin in meiotic chromosome morphogenesis and pairing,” Molecular Biology of the Cell, vol. 20, no. 3, pp. 1030–1047, 2009.
[21]
K. A. Henderson and S. Keeney, “Synaptonemal complex formation: where does it start?” BioEssays, vol. 27, no. 10, pp. 995–998, 2005.
[22]
A. Lynn, R. Soucek, and G. V. B?rner, “ZMM proteins during meiosis: crossover artists at work,” Chromosome Research, vol. 15, no. 5, pp. 591–605, 2007.
[23]
T. Tsubouchi, A. J. MacQueen, and G. S. Roeder, “Initiation of meiotic chromosome synapsis at centromeres in budding yeast,” Genes and Development, vol. 22, no. 22, pp. 3217–3226, 2008.
[24]
M. N. Gladstone, D. Obeso, H. Chuong, and D. S. Dawson, “The synaptonemal complex protein Zip1 promotes bi-orientation of centromeres at meiosis I,” PLoS Genetics, vol. 5, no. 12, Article ID e1000771, 2009.
[25]
A. J. MacQueen and G. S. Roeder, “Fpr3 and Zip3 ensure that initiation of meiotic recombination precedes chromosome synapsis in budding yeast,” Current Biology, vol. 19, no. 18, pp. 1519–1526, 2009.
[26]
M. Shinohara, S. D. Oh, N. Hunter, and A. Shinohara, “Crossover assurance and crossover interference are distinctly regulated by the ZMM proteins during yeast meiosis,” Nature Genetics, vol. 40, no. 3, pp. 299–309, 2008.
[27]
E. J. Lambie and G. S. Roeder, “Repression of meiotic crossing over by a centromere (CEN3) in Saccharomyces cerevisiae,” Genetics, vol. 114, no. 3, pp. 769–789, 1986.
[28]
E. J. Lambie and G. S. Roeder, “A yeast centromere acts in cis to inhibit meiotic gene conversion of adjacent sequences,” Cell, vol. 52, no. 6, pp. 863–873, 1988.
[29]
F. Baudat and A. Nicolas, “Clustering of meiotic double-strand breaks on yeast chromosome III,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 10, pp. 5213–5218, 1997.
[30]
J. L. Gerton, J. DeRisi, R. Shroff, M. Lichten, P. O. Brown, and T. D. Petes, “Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 21, pp. 11383–11390, 2000.
[31]
S. Y. Chen, T. Tsubouchi, B. Rockmill et al., “Global analysis of the meiotic crossover landscape,” Developmental Cell, vol. 15, no. 3, pp. 401–415, 2008.
[32]
P. R. Chua and G. S. Roeder, “Zip2, a meiosis-specific protein required for the initiation of chromosome synapsis,” Cell, vol. 93, no. 3, pp. 349–359, 1998.
[33]
S. Agarwal and G. S. Roeder, “Zip3 provides a link between recombination enzymes and synaptonemal complex proteins,” Cell, vol. 102, no. 2, pp. 245–255, 2000.
[34]
K. A. Henderson and S. Keeney, “Tying synaptonemal complex initiation to the formation and programmed repair of DNA double-strand breaks,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 13, pp. 4519–4524, 2004.
[35]
T. Tsubouchi, H. Zhao, and G. S. Roeder, “The meiosis-specific Zip4 protein regulates crossover distribution by promoting synaptonemal complex formation together with Zip2,” Developmental Cell, vol. 10, no. 6, pp. 809–819, 2006.
[36]
L. Newnham, P. Jordan, B. Rockmill, G. S. Roeder, and E. Hoffmann, “The synaptonemal complex protein, Zip1, promotes the segregation of nonexchange chromosomes at meiosis I,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 2, pp. 781–785, 2010.
[37]
C. Denison, A. D. Rudner, S. A. Gerber, C. E. Bakalarski, D. Moazed, and S. P. Gygi, “A proteomic strategy for gaining insights into protein sumoylation in yeast,” Molecular and Cellular Proteomics, vol. 4, no. 3, pp. 246–254, 2005.
[38]
B. Montpetit, T. R. Hazbun, S. Fields, and P. Hieter, “Sumoylation of the budding yeast kinetochore protein Ndc10 is required for Ndc10 spindle localization and regulation of anaphase spindle elongation,” Journal of Cell Biology, vol. 174, no. 5, pp. 653–663, 2006.
[39]
J. R. Newman, E. Wolf, and P. S. Kim, “A computationally directed screen identifying interacting coiled coils from Saccharomyces cerevisiae,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 24, pp. 13203–13208, 2000.
[40]
J. Wong, Y. Nakajima, S. Westermann et al., “A protein interaction map of the mitotic spindle,” Molecular Biology of the Cell, vol. 18, no. 10, pp. 3800–3809, 2007.
[41]
A. Bardhan, “Complex regulation of sister kinetochore orientation in meiosis-I,” Journal of Biosciences, vol. 35, no. 3, pp. 485–495, 2010.
[42]
G. W. Hooker and G. S. Roeder, “A role for SUMO in meiotic chromosome synapsis,” Current Biology, vol. 16, no. 12, pp. 1238–1243, 2006.
[43]
A. Bardhan, “Many functions of the meiotic cohesin,” Chromosome Research, vol. 18, pp. 909–924, 2010.
[44]
C. Ciferri, A. Musacchio, and A. Petrovic, “The Ndc80 complex: hub of kinetochore activity,” FEBS Letters, vol. 581, no. 15, pp. 2862–2869, 2007.
[45]
K. P. Kim, B. M. Weiner, L. Zhang, A. Jordan, J. Dekker, and N. Kleckner, “Sister cohesion and structural axis components mediate homolog bias of meiotic recombination,” Cell, vol. 143, no. 6, pp. 924–937, 2010.
[46]
M. Pradillo and J. L. Santos, “The template choice decision in meiosis: is the sister important?” Chromosoma, vol. 120, no. 5, pp. 447–454, 2011.
[47]
T. L. Callender and N. M. Hollingsworth, “Mek1 suppression of meiotic double-strand break repair is specific to sister chromatids, chromosome autonomous and independent of Rec8 cohesin complexes,” Genetics, vol. 185, no. 3, pp. 771–782, 2010.