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http://dx.doi.org/10.14348/molcells.2016.0069

Hop2 and Sae3 Are Required for Dmc1-Mediated Double-Strand Break Repair via Homolog Bias during Meiosis  

Cho, Hong-Rae (Department of Life Sciences, Chung-Ang University)
Kong, Yoon-Ju (Department of Life Sciences, Chung-Ang University)
Hong, Soo-Gil (Department of Life Sciences, Chung-Ang University)
Kim, Keun Pil (Department of Life Sciences, Chung-Ang University)
Publication Information
Molecules and Cells / v.39, no.7, 2016 , pp. 550-556 More about this Journal
Abstract
During meiosis, exchange of DNA segments occurs between paired homologous chromosomes in order to produce recombinant chromosomes, helping to increase genetic diversity within a species. This genetic exchange process is tightly controlled by the eukaryotic RecA homologs Rad51 and Dmc1, which are involved in strand exchange of meiotic recombination, with Rad51 participating specifically in mitotic recombination. Meiotic recombination requires an interaction between homologous chromosomes to repair programmed double-strand breaks (DSBs). In this study, we investigated the budding yeast meiosis-specific proteins Hop2 and Sae3, which function in the Dmc1-dependent pathway. This pathway mediates the homology searching and strand invasion processes. Mek1 kinase participates in switching meiotic recombination from sister bias to homolog bias after DSB formation. In the absence of Hop2 and Sae3, DSBs were produced normally, but showed defects in the DSB-to-single-end invasion transition mediated by Dmc1 and auxiliary factors, and mutant strains failed to complete proper chromosome segregation. However, in the absence of Mek1 kinase activity, Rad51-dependent recombination progressed via sister bias in the $hop2{\Delta}$ or $sae3{\Delta}$ mutants, even in the presence of Dmc1. Thus, Hop2 and Sae3 actively modulate Dmc1-dependent recombination, effectively progressing homolog bias, a process requiring Mek1 kinase activation.
Keywords
budding yeast; double-strand breaks; Hop2; recombination; Sae3;
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1 Hong, S., Sung, Y., Yu, M., Lee, M., Kleckner, N., and Kim, K.P. (2013a). The logic and mechanism of homologous recombination partner choice. Mol. Cell 51, 440-453.   DOI
2 Hong, S., and Kim, K.P. (2013b). Shu1 Promotes Homolog Bias of Meiotic Recombination in Saccharomyces cerevisiae. Mol. Cells 36, 446-454.   DOI
3 Hong, S., Choi, E.H., and Kim, K.P. (2015). Ycs4 is required for efficient double-strand break formation and homologous recombination during meiosis. J. Microbiol. Biotechnol. 25, 1026-1035.   DOI
4 Hunter, N., and Kleckner, N. (2001). The single-end invasion: an asymmetric intermediate at the double-strand break to doubleholliday junction transition of meiotic recombination. Cell 106, 59-70.   DOI
5 Kang, H.A., Shin, H.C., Kalantzi, A.S., Toseland, C.P., Kim, H.M., Gruber, S., Peraro, M.D., and Oh, B.H. (2015). Crystal structure of Hop2-Mnd1 and mechanistic insights into its role in meiotic recombination. Nucleic Acids Res. 43, 3841-3856.   DOI
6 Keeney, S. (2001). Mechanism and control of meiotic recombination initiation. Curr. Topics Dev. Biol. 52, 1-53.   DOI
7 Kim, K.P., Weiner, B.M., Zhang, L., Jordan, A., Dekker, J., and Kleckner, N. (2010). Sister cohesion and structural axis components mediate homolog bias of meiotic recombination. Cell 143, 924-937.   DOI
8 Koszul, R., Kim, K.P., Prentiss, M., Kleckner, N., and Kameoka, S. (2008). Meiotic chromosomes move by linkage to dynamic actin cables with transduction of force through the nuclear envelope. Cell 133, 1188-1201.   DOI
9 Lao, J.P., Cloud, V., Huang, C.C., Grubb, J., Thacker, D., Lee, C.Y., Dresser, M.E., Hunter, N., and Bishop, D.K. (2013). Meiotic crossover control by concerted action of Rad51-Dmc1 in homolog template bias and robust homeostatic regulation. PLoS genetics 9, e1003978.   DOI
10 Lee, M.S., Yu, M., Kim, K.Y., Park, G.H., Kwack, K.B., and Kim, K.P. (2015a). Functional validation of rare human genetic variants involved in homologous recombination using Saccharomyces cerevisiae. PLoS One 10, e0124152.   DOI
11 Lee, M.S., Yoon, S.W., and Kim, K.P. (2015b). Mitotic cohesin subunit Mcd1 regulates the progression of meiotic recombination in budding yeast. J. Microbiol. Biotechnol. 25, 598-605.   DOI
12 Leu, J.Y., Chua, P.R., and Roeder, G.S. (1998). The meiosis-Hop2 protein of S. cerevisiae ensures synapsis between homologous chromosomes. Cell 94, 375-386.   DOI
13 Lukaszewicz, A., Shodhan, A., and Loidl, J. (2015). Exo1 and Mre11 execute meiotic DSB end resection in the protist Tetrahymena. DNA Repair 35, 137-143.   DOI
14 Mancera, E., Bourgon, R., Brozzi, A., Huber, W., Steinmetz, L. M. (2008). High-resolution mapping of meiotic crossovers and noncrossovers in yeast. Nature 454, 479-485.   DOI
15 Martini, E., Diaz, R. L., Hunter, N., Keeney, S. (2006). Crossover homeostasis in yeast meiosis. Cell 156, 285-95.
16 Neale, M.J., and Keeney, S. (2006). Clarifying the mechanics of DNA strand exchange in meiotic recombination. Nature 442, 153-158.   DOI
17 Niu, H., Li, X., Job, E., Park, C., Moazed, D., Gygi, S.P., and Hollingsworth, N.M. (2007). Mek1 kinase is regulated to suppress double-strand break repair between sister chromatids during budding yeast meiosis. Mol. Cell. Biol. 27, 5456-5467.   DOI
18 Niu, H., Wan, L., Busygina, V., Kwon, Y., Allen, J.A., Li, X., Kunz, R.C., Kubota, K., Wang, B., Sung, P., et al. (2009). Regulation of meiotic recombination via Mek1-mediated Rad54 phosphorylation. Mol. Cell 36, 393-404.   DOI
19 Oh, S.D., Lao, J.P., Hwang, P.Y., Taylor, A.F., Smith, G.R., and Hunter, N. (2007). BLM ortholog, Sgs1, prevents aberrant crossing-over by suppressing formation of multichromatid joint molecules. Cell 130, 259-272.   DOI
20 Petukhova, G.V., Romanienko, P.J., Camerini-Otero, R. D. (2003). The Hop2 protein has a direct role in promoting interhomolog interactions during mouse meiosis. Dev. Cell 5, 927-936.   DOI
21 Petukhova, G.V., Pezza, R.J., Vanevski, F., Ploquin, M., Masson, J.Y., and Camerini-Otero, R.D. (2005). The Hop2 and Mnd1 proteins act in concert with Rad51 and Dmc1 in meiotic recombination. Nat. Struct. Mol. Biol. 12, 449-453.   DOI
22 Pezza, R.J., Voloshin, O.N., Vanevski, F., and Camerini-Otero, R.D. (2007). Hop2/Mnd1 acts on two critical steps in Dmc1-promoted homologous pairing. Genes Dev. 21, 1758-1766.   DOI
23 Pezza, R.J., Voloshin, O.N., Volodin, A.A., Boateng, K.A., Bellani, M.A., Mazin, A.V., and Camerini-Otero, R.D. (2014). The dual role of HOP2 in mammalian meiotic homologous recombination. Nucleic Acids Res. 42, 2346-2357.   DOI
24 Schwacha, A., and Kleckner, N. (1997). Interhomolog bias during meiotic recombination: meiotic functions promote a highly differentiated interhomolog-only pathway. Cell 90, 1123-1135.   DOI
25 Shinohara, A., Gasior, S., Ogawa, T., Kleckner, N., and Bishop, D. (1997). Saccharomyces cerevisiae recA homologues RAD51 and DMC1 have both distinct and overlapping roles in meiotic recombination. Genes Cells 10, 615-629.
26 Tracy, L.C., and Nancy, M.H. (2010). Mek1 suppression of meiotic double-strand break repair is specific to sister chromatids, chromosome autonomous and independent of Rec8 cohesin complexes. Genetics 185, 771-782.   DOI
27 Tsubouchi, H., and Roeder, G.S. (2002). The Mnd1 protein forms a complex with hop2 to promote homologous chromosome pairing and meiotic double-strand break repair. Mol. Cell. Biol. 22, 3078-3088.   DOI
28 Tsubouchi, H., and Roeder, G.S. (2004). The budding yeast mei5 and sae3 proteins act together with dmc1 during meiotic recombination. Genetics 168, 1219-1230.   DOI
29 Zakharyevich, K., Ma, Y., Tang, S., Hwang, P.Y., Boiteux, S., and Hunter, N. (2010). Temporally and biochemically distinct activities of Exo1 during meiosis: double-strand break resection and resolution of double Holliday junctions. Mol. Cell 40, 1001-1015.   DOI
30 Allers, T., Lichten, M. (2001). Differential timing and control of noncrossover and crossover recombination during meiosis. Cell 106, 47-57.   DOI
31 Borner, G.V., Kleckner, N., and Hunter, N. (2004). Crossover/noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell 117, 29-45.   DOI
32 Busygina, V., Sehorn, M.G., Shi, I.Y., Tsubouchi, H., Roeder, G.S., and Sung, P. (2008). Hed1 regulates Rad51-mediated recombination via a novel mechanism. Genes Dev. 22, 786-795.   DOI
33 Cannavo, E., and Cejka, P. (2014). Sae2 promotes dsDNA endonuclease activity within Mre11-Rad50-Xrs2 to resect DNA breaks. Nature 514, 122-125.   DOI
34 Chan, Y.L., Brown, M.S., Qin, D., Handa, N., and Bishop, D.K. (2014). The third exon of the budding yeast meiotic recombination gene HOP2 is required for calcium-dependent and recombinase Dmc1-specific stimulation of homologous strand assimilation. J. Biol. Chem. 289, 18076-18086.   DOI
35 Chi, P., San Filippo, J., Sehorn, M.G., Petukhova, G.V., and Sung, P. (2007). Bipartite stimulatory action of the Hop2-Mnd1 complex on the Rad51 recombinase. Genes Dev. 21, 1747-1757.   DOI
36 Ferrari, S.R., Grubb, J., and Bishop, D.K. (2009). The Mei5-Sae3 protein complex mediates Dmc1 activity in Saccharomyces cerevisiae. J. Biol. Chem. 284, 11766-11770.   DOI
37 Garcia, V., Phelps, S.E., Gray, S., and Neale, M.J. (2011). Bidirectional resection of DNA double-strand breaks by Mre11 and Exo1. Nature 479, 241-244.   DOI
38 Gerton, J.L., and Hawley, R.S. (2005). Homologous chromosome interactions in meiosis: diversity amidst conservation. Nat. Rev. Genet. 6, 477-487.   DOI
39 Hayase, A., Takagi, M., Miyazaki, T., Oshiumi, H., Shinohara, M., and Shinohara, A. (2004). A protein complex containing Mei5 and Sae3 promotes the assembly of the meiosis-specific RecA homolog Dmc1. Cell 119, 927-940.   DOI
40 Henry, J.M., Camahort, R., Rice, D.A., Florens, L., Swanson, S.K., Washburn, M.P., and Gerton, J.L. (2006). Mnd1/Hop2 facilitates Dmc1-dependent interhomolog crossover formation in meiosis of budding yeast. Mol. Cell. Biol. 26, 2913-2923.   DOI