SUMO Localizes to the Central Element of Synaptonemal Complex and Is Required for the Full Synapsis of Meiotic Chromosomes in Budding Yeast
The synaptonemal complex (SC) is a widely conserved structure that mediates the intimate alignment of homologous chromosomes during meiotic prophase and is required for proper homolog segregation at meiosis I. However, fundamental details of SC architecture and assembly remain poorly understood. The coiled-coil protein, Zip1, is the only component whose arrangement within the mature SC of budding yeast has been extensively characterized. It has been proposed that the Small Ubiquitin-like MOdifier, SUMO, plays a role in SC assembly by linking chromosome axes with Zip1's C termini. The role of SUMO in SC structure has not been directly tested, however, because cells lacking SUMO are inviable. Here, we provide direct evidence for SUMO's function in SC assembly. A meiotic smt3 reduction-of-function strain displays reduced sporulation, abnormal levels of crossover recombination, and diminished SC assembly. SC structures are nearly absent when induced at later meiotic time points in the smt3 reduction-of-function background. Using Structured Illumination Microscopy we furthermore determine the position of SUMO within budding yeast SC structure. In contrast to previous models that positioned SUMO near Zip1's C termini, we demonstrate that SUMO lies at the midline of SC central region proximal to Zip1's N termini, within a subdomain called the “central element”. The recently identified SUMOylated SC component, Ecm11, also localizes to the SC central element. Finally, we show that SUMO, Ecm11, and even unSUMOylatable Ecm11 exhibit Zip1-like ongoing incorporation into previously established SCs during meiotic prophase and that the relative abundance of SUMO and Ecm11 correlates with Zip1's abundance within SCs of varying Zip1 content. We discuss a model in which central element proteins are core building blocks that stabilize the architecture of SC near Zip1's N termini, and where SUMOylation may occur subsequent to the incorporation of components like Ecm11 into an SC precursor structure.
Vyšlo v časopise:
SUMO Localizes to the Central Element of Synaptonemal Complex and Is Required for the Full Synapsis of Meiotic Chromosomes in Budding Yeast. PLoS Genet 9(10): e32767. doi:10.1371/journal.pgen.1003837
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1003837
Souhrn
The synaptonemal complex (SC) is a widely conserved structure that mediates the intimate alignment of homologous chromosomes during meiotic prophase and is required for proper homolog segregation at meiosis I. However, fundamental details of SC architecture and assembly remain poorly understood. The coiled-coil protein, Zip1, is the only component whose arrangement within the mature SC of budding yeast has been extensively characterized. It has been proposed that the Small Ubiquitin-like MOdifier, SUMO, plays a role in SC assembly by linking chromosome axes with Zip1's C termini. The role of SUMO in SC structure has not been directly tested, however, because cells lacking SUMO are inviable. Here, we provide direct evidence for SUMO's function in SC assembly. A meiotic smt3 reduction-of-function strain displays reduced sporulation, abnormal levels of crossover recombination, and diminished SC assembly. SC structures are nearly absent when induced at later meiotic time points in the smt3 reduction-of-function background. Using Structured Illumination Microscopy we furthermore determine the position of SUMO within budding yeast SC structure. In contrast to previous models that positioned SUMO near Zip1's C termini, we demonstrate that SUMO lies at the midline of SC central region proximal to Zip1's N termini, within a subdomain called the “central element”. The recently identified SUMOylated SC component, Ecm11, also localizes to the SC central element. Finally, we show that SUMO, Ecm11, and even unSUMOylatable Ecm11 exhibit Zip1-like ongoing incorporation into previously established SCs during meiotic prophase and that the relative abundance of SUMO and Ecm11 correlates with Zip1's abundance within SCs of varying Zip1 content. We discuss a model in which central element proteins are core building blocks that stabilize the architecture of SC near Zip1's N termini, and where SUMOylation may occur subsequent to the incorporation of components like Ecm11 into an SC precursor structure.
Zdroje
1. BhallaN, DernburgAF (2008) Prelude to a division. Annu Rev Cell Dev Biol 24: 397–424.
2. ZicklerD, KlecknerN (1998) The leptotene-zygotene transition of meiosis. Annu Rev Genet 32: 619–697.
3. ZicklerD, KlecknerN (1999) Meiotic chromosomes: integrating structure and function. Annu Rev Genet 33: 603–754.
4. PageSL, HawleyRS (2004) The genetics and molecular biology of the synaptonemal complex. Annu Rev Cell Dev Biol 20: 525–558.
5. MosesMJ (1968) Synaptonemal complex. Annu Rev Genet 2: 363–412.
6. SolariAJ, MosesMJ (1973) The structure of the central region in the synaptonemal complexes of hamster and cricket spermatocytes. J Cell Biol 56: 145–152.
7. SmithAV, RoederGS (1997) The yeast Red1 protein localizes to the cores of meiotic chromosomes. J Cell Biol 136: 957–967.
8. SymM, EngebrechtJ, RoederGS (1993) Zip1 is a synaptonemal complex protein required for meiotic chromosome synapsis. Cell 72: 365–378.
9. SymM, RoederGS (1995) Zip1-induced changes in synaptonemal complex structure and polycomplex assembly. J Cell Biol 128: 455–466.
10. DongH, RoederGS (2000) Organization of the yeast Zip1 protein within the central region of the synaptonemal complex. J Cell Biol 148: 417–426.
11. AndersonLK, RoyerSM, PageSL, McKimKS, LaiA, et al. (2005) Juxtaposition of C(2)M and the transverse filament protein C(3)G within the central region of Drosophila synaptonemal complex. Proc Natl Acad Sci U S A 102: 4482–4487.
12. LiuJ-G, YuanL, BrundellE, BjorkrothB, DaneholtB, et al. (1996) Localization of the N-terminus of SCP1 to the central element of the synaptonemal complex and evidence for direct interactions between the N-termini of SCP1 molecules organized head-to-head. Exp Cell Res 226: 11–19.
13. SchmekelK, MeuwissenRLJ, DietrichAJJ, VinkACG, MarleJv, et al. (1996) Organization of SCP1 protein molecules within synaptonemal complexes of the rat. Exp Cell Res 227: 20–30.
14. AgarwalS, RoederGS (2000) Zip3 provides a link between recombination enzymes and synaptonemal complex proteins. Cell 102: 245–255.
15. Bolcun-FilasE, CostaY, SpeedR, TaggartM, BenaventeR, et al. (2007) SYCE2 is required for synaptonemal complex assembly, double strand break repair, and homologous recombination. J Cell Biol 176: 741–747.
16. Bolcun-FilasE, HallE, SpeedR, TaggartM, GreyC, et al. (2009) Mutation of the mouse Syce1 gene disrupts synapsis and suggests a link between synaptonemal complex structural components and DNA repair. PLoS Genet 5: e1000393.
17. ChuaPR, RoederGS (1998) Zip2, a meiosis-specific protein required for the initiation of chromosome synapsis. Cell 93: 349–359.
18. HamerG, GellK, KouznetsovaA, NovakI, BenaventeR, et al. (2006) Characterization of a novel meiosis-specific protein within the central element of the synaptonemal complex. J Cell Sci 119: 4025–4032.
19. HookerGW, RoederGS (2006) A role for SUMO in meiotic chromosome synapsis. Curr Biol 16: 1238–1243.
20. PageSL, KhetaniRS, LakeCM, NielsenRJ, JeffressJK, et al. (2008) Corona is required for higher-order assembly of transverse filaments into full-length synaptonemal complex in Drosophila oocytes. PLoS Genet 4: e1000194.
21. TsubouchiT, ZhaoH, RoederGS (2006) The meiosis-specific Zip4 protein regulates crossover distribution by promoting synaptonemal complex formation together with Zip2. Dev Cell 10: 809–819.
22. DaviesOR, MamanJD, PellegriniL (2012) Structural analysis of the human SYCE2-TEX12 complex provides molecular insights into synaptonemal complex assembly. Open Biol 2: 120099.
23. SchrammS, FrauneJ, NaumannR, Hernandez-HernandezA, HoogC, et al. (2011) A novel mouse synaptonemal complex protein is essential for loading of central element proteins, recombination, and fertility. PLoS Genet 7: e1002088.
24. JeffressJK, PageSL, RoyerSK, BeldenED, BlumenstielJP, et al. (2007) The formation of the central element of the synaptonemal complex may occur by multiple mechanisms: the roles of the N- and C-terminal domains of the Drosophila C(3)G protein in mediating synapsis and recombination. Genetics 177: 2445–2456.
25. ChengC-H, LoY-H, LiangS-S, TiS-C, LinF-M, et al. (2006) SUMO modification control assembly of synaptonemal complex and polycomplex in meiosis of Saccharomyces cerevisiae. Genes Dev 20: 2067–2081.
26. de CarvalhoCE, ColaiacovoMP (2006) SUMO-mediated regulation of synaptonemal complex formation during meiosis. Genes Dev 20: 1986–1992.
27. EichingerCS, JentschS (2010) Synaptonemal complex formation and meiotic checkpoint signaling are linked to the lateral element protein Red1. Proc Natl Acad Sci U S A 107: 11370–11375.
28. WattsFZ, HoffmannE SUMO meets meiosis: an encounter at the synaptonemal complex: SUMO chains and sumoylated proteins suggest that heterogeneous and complex interactions lie at the centre of the synaptonemal complex. Bioessays 33: 529–537.
29. HumphryesN, LeungW, ArgunhanB, TerentyevY, DvorackovaM, et al. (2013) The Ecm11-Gmc2 Complex Promotes Synaptonemal Complex Formation Through Assembly of Transverse Filaments in Budding Yeast. PLoS Genet 9: e1003194.
30. ZavecAB, CominoA, LenassiM, KomelR (2008) Ecm11 protein of yeast Saccharomyces cerevisiae is regulated by sumoylation during meiosis. FEMS Yeast Res 8: 64–70.
31. ZavecAB, LesnikU, KomelR, CominoA (2004) The Saccharomyces cerevisiae gene ECM11 is a positive effector of meiosis. FEMS Microbiol Lett 241: 193–199.
32. GuacciV, KoshlandD, StrunnikovA (1997) A direct link between sister chromatid cohesion and chromosome condensation revealed through the analysis of MCD1 in S. cerevisiae. Cell 91: 47–57.
33. KleinF, MahrP, GalovaM, BuonomoS, NasmythK (1999) A central role for cohesins in sister chromatid cohesion, the formation of axial elements and recombination during yeast meiosis. Cell 98: 91–103.
34. MichaelisC, CioskR, NasmythK (1997) Cohesins: chromosomal proteins that prevent premature separation of sister chromatids. Cell 91: 35–45.
35. ShirkK, JinH, GiddingsTHJr, WineyM, YuHG The Aurora kinase Ipl1 is necessary for spindle pole body cohesion during budding yeast meiosis. J Cell Sci 124: 2891–2896.
36. StraightPD, GiddingsTHJr, WineyM (2000) Mps1p regulates meiotic spindle pole body duplication in addition to having novel roles during sporulation. Mol Biol Cell 11: 3525–3537.
37. MoensPB, RapportE (1971) Spindles, spindle plaques, and meiosis in the yeast Saccharomyces cerevisiae (Hansen). J Cell Biol 50: 344–361.
38. FarmerS, HongEJ, LeungWK, ArgunhanB, TerentyevY, et al. (2012) Budding yeast Pch2, a widely conserved meiotic protein, is involved in the initiation of meiotic recombination. PLoS One 7: e39724.
39. HoHC, BurgessSM (2011) Pch2 acts through Xrs2 and Tel1/ATM to modulate interhomolog bias and checkpoint function during meiosis. PLoS Genet 7: e1002351.
40. San-SegundoP, RoederGS (1999) Pch2 links chromatin silencing to meiotic checkpoint control. Cell 97: 313–324.
41. WuHY, BurgessSM (2006) Two distinct surveillance mechanisms monitor meiotic chromosome metabolism in budding yeast. Curr Biol 16: 2473–2479.
42. MitraN, RoederGS (2007) A novel nonnull ZIP1 allele triggers meiotic arrest with synapsed chromosomes in Saccharomyces cerevisiae. Genetics 176: 773–787.
43. SymM, RoederGS (1994) Crossover interference is abolished in the absence of a synaptonemal complex protein. Cell 79: 283–292.
44. WhiteEJ, CowanC, CandeWZ, KabackDB (2004) In vivo analysis of synaptonemal complex formation during yeast meiosis. Genetics 167: 51–63.
45. BornerGV, BarotA, KlecknerN (2008) Yeast Pch2 promotes domainal axis organization, timely recombination progression, and arrest of defective recombinosomes during meiosis. Proc Natl Acad Sci U S A 105: 3327–3332.
46. Voelkel-MeimanK, MoustafaSS, LefrancoisP, VilleneuveAM, MacQueenAJ (2012) Full-Length Synaptonemal Complex Grows Continuously during Meiotic Prophase in Budding Yeast. PLoS Genet 8: e1002993.
47. KlugH, XaverM, ChauguleVK, KoidlS, MittlerG, KleinF, PichlerA (2013) Ubc9 Sumoylation Controls SUMO Chain Formation and Meiotic Synapsis in Saccharomyces cerevisiae. Mol Cell 50: 625–636.
48. FalkJE, ChanAC, HoffmannE, HochwagenA (2010) A Mec1- and PP4-dependent checkpoint couples centromere pairing to meiotic recombination. Dev Cell 19: 599–611.
49. NewnhamL, JordanP, RockmillB, RoederGS, HoffmannE (2009) The synaptonemal complex protein, Zip1, promotes the segregation of nonexchange chromosomes at meiosis I. PNAS (epub)
50. LinFM, LaiYJ, ShenHJ, ChengYH, WangTF (2009) Yeast axial-element protein, Red1, binds SUMO chains to promote meiotic interhomologue recombination and chromosome synapsis. EMBO J 29: 586–596.
51. de CarvalhoCE, ColaiacovoMP (2006) SUMO-related regulation of synaptonemal complex formation during meiosis. Genes Dev 20: 1986.
52. TungK-S, RoederGS (1998) Meiotic chromosome morphology and behavior in zip1 mutants of Saccharomyces cerevisiae. Genetics 149: 817–832.
53. RockmillB, EngebrechtJA, ScherthanH, LoidlJ, RoederGS (1995) The yeast MER2 gene is required for chromosome synapsis and the initiation of meiotic recombination. Genetics 141: 49–59.
54. GoldsteinAL, McCuskerJH (1999) Three new dominant drug resistance cassettes for gene disruption in Saccharomyces cerevisiae. Yeast 15: 1541–1553.
55. RockmillB, LambieEJ, RoederGS (1991) Spore enrichment. Meth Enzymol 194: 146–149.
56. PerkinsDD (1949) Biochemical Mutants in the Smut Fungus Ustilago Maydis. Genetics 34: 607–626.
57. HongEE, RoederGS (2002) A role for Ddc1 in signaling meiotic double-strand breaks at the pachytene checkpoint. Genes Dev 16: 363–376.
58. BenjaminKR, ZhangC, ShokatKM, HerskowitzI (2003) Control of landmark events in meiosis by the CDK Cdc28 and the meiosis-specific kinase Ime2. Genes Dev 17: 1524–1539.
59. PapazianHP (1952) The analysis of tetrad data. Genetics 37: 175–188.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2013 Číslo 10
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Dominant Mutations in Identify the Mlh1-Pms1 Endonuclease Active Site and an Exonuclease 1-Independent Mismatch Repair Pathway
- Eleven Candidate Susceptibility Genes for Common Familial Colorectal Cancer
- The Histone H3 K27 Methyltransferase KMT6 Regulates Development and Expression of Secondary Metabolite Gene Clusters
- A Mutation in the Gene in Labrador Retrievers with Hereditary Nasal Parakeratosis (HNPK) Provides Insights into the Epigenetics of Keratinocyte Differentiation